Nuclear Medicine and Biology xxx (2015) xxx–xxx

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Nuclear Medicine and Biology

journal homepage: www.elsevier.com/locate/nucmedbio

18
F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer
imaging: which is better? A literature revision
Laura Evangelista a,⁎, Anna Rita Cervino a, Andrea Guttilla b, Fabio Zattoni b, Vincenzo Cuccurullo c, Luigi Mansi c
a
Radiotherapy and Nuclear Medicine Unit, Oncological Institute of Veneto IOV-IRCCS, Padua, Italy
b
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padua, Italy
c
Nuclear Medicine, Second University of Naples, Napoli, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: The present review was conceived for describing the differences in biodistribution and diagnostic
Received 6 October 2014 performance of two types of 18 F-radiolabeled choline for positron emission tomography (PET) imaging in pros-
Received in revised form 22 December 2014 tate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC).
Accepted 28 December 2014 Materials and methods: A collection of published data about two radiopharmaceutical agents was made by using
Available online xxxx
PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed.
Results: FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for
Keywords:
Diagnostic accuracy
basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metas-
Fluoethylcholine tasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Con-
Fluoromethylcholine versely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA
PET imaging value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and
Prostate cancer 96% for FCH and between 62% and 85.7% for FEC).
Conclusions: In according with the available information, FCH appears to be a more appropriate radiocompound
as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for
the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential.
Advances in knowledge and implication for patient care: FCH seems to be an appropriate radiopharmaceutical agent
as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of
a serial increase in PSA value and their performance improves when a correct preparation and acquisition
protocol is employed.
© 2014 Elsevier Inc. All rights reserved.

1. Introduction accumulates in a variety of tumor cells, including PCa. Radiolabeled-

The use of positron emission tomography (PET) tracers for the
evaluation of urogenital diseases has been expanding in recent years,
particularly for prostate cancer (PCa). Although Magnetic Resonance
(MR) may also play a clinical role, radionuclide functional imaging has
generated great interest, being able to surpass the limits of conventional
imaging, such as computed tomography (CT) and bone scan (BS). Thus,
it is gaining importance for both clinical management and drug
development for PCa.
The currently available PET tracers for PCa include 18 F-sodium
fluoride (18 F-NaF), 11C-acetate, 11C-choline, and 18 F-choline. Interest
in radiolabeled-choline tracers for differentiating and for localizing ma-
lignancies has been increasing, because phosphocholine (Pcho)
⁎ Corresponding author. Radiotherapy and Nuclear Medicine Unit, Veneto Institute of
Oncology IOV-IRCCS, Gattamelata Street, 64 Padova, Italy. Tel.: +39 049 821 7997;
fax: +39 049 821 2205.
E-mail address: laura.evangelista@ioveneto.it (L. Evangelista).
choline analogs are entrapped by PCa cells by choline transporters and
are intracellularly phosphorylated by choline kinase (CK), which is
strongly associated with phospholipid metabolism [1–4] (Fig. 1). Both
11
C-choline and 18 F-radiolabeled-choline have been extensively used
for imaging applications in PCa patients, mostly in Europe and Japan
[5]; further growth has been recorded after the approval of production
and use of 11C-choline for PET imaging in recurrent PCa by the US
Food and Drug Administration, announced on September 2012 [6].
Current use of 11C-choline PET/CT in PCa patients has mainly been
aimed at the early detection of disease recurrence, leading to a possible
change in patient management. In particular, it has been shown to im-
prove the assessment of disease spreading with respect to local and dis-
tant metastasis as well as bone involvement [7] and to avoid the futile
use of radiotherapy in the prostatic bed, thus reducing the rate of related
morbidity [8]. Nevertheless, the use of 11C-choline is not a widely
available option because it has a short half-life of 20 min. This limit
has stimulated the development of 18 F-labeled choline. The practical
advantages of working with 18 F (e.g. its longer half-life that allows
long-time storage and long-distance transportation; its shorter

http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
0969-8051/© 2014 Elsevier Inc. All rights reserved.

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
2 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx

positron range gives a quality of image with a slightly higher spatial res-
olution) led Hara et al. [9] to synthesize and to evaluate 2-[ 18 F]
fluoroethyldimethyl-2-hydroxyethylammonium (FEC) as a choline ana-
log. They demonstrated in vitro that FEC is incorporated into tumor cells
by an active transport, then phosphorylated inside the cells yielding
phosphoryl- 18 F-FEC and finally integrated into phospholipids. Later,
Hara et al. [10] showed in vivo no difference between FEC uptake and
11
C-choline uptake in PCa. Some years later, DeGrado et al. [11]
synthesized fluoromethyl-dimethyl-2-hydroxyethylammonium
(fluorocholine or FCH). FCH differs from FEC by a single methylene
group between the nitrogen atom and the carbon bearing the fluorine
atom (Fig. 2); this small structural difference is associated with an FEC
uptake reduction of 80% in PC-3 prostate cancer cells. Furthermore,
whereas FCH showed equivalent in vitro phosphorylation with choline,
FEC was more poorly phosphorylated by CK. DeGrado et al. [11] report-
ed a steric hindrance of CK-catalyzed phosphorylation for analogs with
fluorine containing substituents larger than the fluoromethyl group. As
further information affecting pharmacokinetics, Uusijärvi et al. [12]
demonstrated a different biodistribution of 18 F-choline between 0
and 1 h after injection in 4 patients with PCa recurrence after radical
prostatectomy: the uptake decreases in kidneys and in spleen while it
increases in liver, salivary glands and in the tumor [12]. In any case,
the authors reported no clear information about the type of 18 F-
labeled choline compound.
In the present review, we have selectively collected and critically
evaluated published articles in order to assess the differences between
FEC and FCH PET/CT scans in PCa patients, in both acquisition protocols
and diagnostic performance.
2. Materials and methods
2.1. Literature research
A computer literature search of studies on FCH and/or FEC PET or
PET/CT in PCa patients performed between January 2000 and Septem-
ber 2014 was carried out. MEDLINE databases, such as Pubmed, Web
of Knowledge and TripDatabase, were consulted using the following
key words: “fluoromethylcholine” AND “prostate”; “fluoroethylcholine”
AND “prostate”. Moreover, some limits were applied to the search strat-
egy, such as species (human), article type (original articles, comparative
studies, multicenter study) and language (English).
MEDLINE research produced 78 scientific papers: in particular, 53
with “fluoromethylcholine”, of which 28 also contained “prostate”,
and 25 with “fluoroethylcholine”, of which four also contained “pros-
tate”. Abstracts, reviews, clinical reports and editor comments were ex-
cluded. The references of articles found in the literature search were also
examined to find additional reports that met the inclusion criteria. Only
28 articles met the inclusion criteria (Table 1). In particular, 20 studies
included PET or PET/CT with FCH, three with FEC and one study with
both tracers. On the contrary, five studies did not specify what type of
18
F-labeled choline compound was injected, indifferently reporting
the acronym FCH or FC. For information about the source of radiophar-
maceutical, the investigators were contacted. Fig. 3 illustrates the flow-
chart of selected studies.
PET or PET/CT was performed for initial staging, re-staging, treat-
ment monitoring and treatment planning. In most cases, prospective
studies were included (n = 19), and therefore approved by the local

Choline Cell
membrane
Choline transporters

SP1
Cytoplasm

GP
RAF Choline
PI3K C
RALGDS
GPC-PDE

HIF1 CH
K

1-acylglycero-
AP1
phosphocholine

SP1 RALGDS RAS PLA PCho

2
RAF

CC
RAF RAS
T
PC-PLD
SP1
PLA
2
RAF
CDP-
PI3K Cho ERK

JNK
FA DAG
CHPT
1

SREBP

Cell
membrane Ptd Cho
Nucleus

Fig. 1. Choline metabolic pathway.

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx
OH
18F-fluorocholine (FCH) 18F
N+
18F
18F-fluoroetylcholine (FEC)
N+
Fig. 2. Chemical structures of fluoethylcholine and fluoromethylcholine.
ethical committees. The selected articles were published from 2006 to
2014. A total of 2147 PCa patients were included and all of them well
tolerated 18 F-radiolabeled-choline without reporting adverse events.
Five-hundred thirty six patients were at initial staging, and 1611 at
restaging or at treatment planning. FCH was injected in 338 and 1164
patients, while FEC was injected in 20 and 139 patients, respectively
for basal staging and re-staging. For the residual 383 patients, the type
of 18 F-labeled choline was not well addressed (178 and 308 patients
at initial staging and at re-staging of disease, respectively).
3. Results
Each article was evaluated on the basis of the study population
(number of patients, patient preparation, injection time, acquisition
protocol) and the study design (prospective, retrospective and
comparative).
3.1. FEC PET or PET/CT in clinical practice
FEC PET was employed in four original papers [13–16]. Graute et al.
[13] performed PET/CT scans both with FEC and with FCH in 82 PCa pa-
tients (n = 25 with FCH and n = 57 with FEC). The authors declared
that both FC compounds showed similar in vivo properties. They dem-
onstrated a detection recurrence rate of 62% for FEC/FCH PET/CT. Two
papers [14,15] evaluated the accuracy of FEC PET/CT in the detection
of lymph node metastases in PCa patients; while the paper of
Würschmidt et al. [16] was related to the planning of radiation treat-
ment. In particular, Tilki et al. [14] and Steuber et al. [15] did not find
any data supporting the use of FEC PET/CT in clinical practice for
lymph node evaluation. The authors reported a sensitivity of 0% and
39.7%, respectively. In particular, Tilki et al. [14] found that the sensitiv-
ity of FEC PET/CT for lymph node assessment was higher when PSA level
was N2 ng/mL as compared to a PSA level b2 ng/mL (42.4% vs. 28.3%, re-
spectively). Steuber et al. [15] showed that FEC PET/CT missed lesions
with a diameter b 10 mm and reported that the potential disadvantages
for FEC in lymph node detection are, firstly, elevated secretion into uri-
nary system and, secondly, the shorter residence time in the blood that
may limit their diffusion into poorly perfused areas. Finally,
Würschmidt et al. [16] clearly demonstrated the efficacy of PET/CT
with FEC in planning radiotherapy.
3.2. FCH PET or PET/CT in clinical practice
Since 2006, 16 prospective studies were published about FCH PET/
CT: five of them enrolled a large sample of patients (from 100 to 250;
[17–21]), while the residual studies considered a limited number of
subjects (from 15 to 56; [22–26]). The prospective studies with the larg-
est population (number ranged between 100 and 250 patients) were
Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
3
authored by Poulsen et al. [17], Beheshti et al. [18,19], and Husarik
et al. [20], who reported an overall sensitivity of FCH PET/CT for the de-
tection of primary or recurrent PCa of 73.2%, 66%, 59.5% and 83% respec-
tively, while Cimitan et al. [21] did not report any data about sensitivity.
Poulsen et al. [17] and Beheshti et al. [18] focused their attention on ini-
tial lymph node evaluation, demonstrating conflicting results. Accord-
ing to the first study, FCH PET/CT was not ideal for the lymph node
staging (sensitivity = 56.2%; specificity = 94%), while on the basis of
the second report, FCH PET/CT was considered a sensitive instrument
OH for lymph node detection (sensitivity = 66%). Husarik et al. [20] showed
the highest overall sensitivity (n = 111 subjects, 86%) for the recurrence
of disease but they agreed with the low sensitivity in detecting lymph
node metastases at initial staging (sensitivity = 20%). Wetter et al.
[22] demonstrated that FCH PET/MR gives the advantage of combining
high resolution images, functional studies and metabolic/molecular im-
aging in PCa patients, but the data are still preliminary. Similar to the
previous results, the analysis of small sample studies demonstrated
some disagreements in sensitivity. Poulsen et al. [23] attributed high
sensitivity, specificity, positive predictive value (PPV) and negative pre-
dictive value (NPV) for patient-based lymph node staging (100%, 95%,
75%, and 100%, respectively) to FCH PET/CT, while Hacker et al. [24]
demonstrated that FCH PET/CT missed lymph node detection in nine pa-
tients, due to the limitation of the scanner’s spatial resolution. Last year,
Buchegger et al. [26] reported an excellent agreement between FCH and
11
C-acetate PET/CT in recurrent PCa patients, thus demonstrating that
both the radiopharmaceutical agents are interchangeable. Moreover,
Kwee et al. [25] showed a link between volumetric measurement of
tumor choline activity and the prognosis of metastatic PCa. As clear ev-
idence of the importance of the inclusion criteria in determining a dif-
ferent diagnostic accuracy, it is interesting to compare the two papers
published, at different times, by Poulsen et al. [17,23]. In the paper pub-
lished in 2010, the authors reported values of 100%, 95%, 75%, and 100%,
respectively in sensitivity, specificity, PPV and NPV for patient-based
lymph node staging when evaluating 25 consecutive males with
newly diagnosed PCa (Gleason score N 6, and/or PSA N 10 ng/mL, and/
or T3 cancer). Completely different results derived by the same group
when analyzing a wider population including 210 intermediate or
high-risk patients [17]. Sensitivity, specificity, PPV, and NPV were
73.2%, 87.6%, 58.8% and 93.1%, respectively. Corresponding values for
LN-based analyses were 56.2%, 94%, 40.2%, and 96.8%, respectively, dis-
couraging a routine use of FCH for primary lymph node staging in pa-
tients with PCa.
Only four retrospective studies were considered in the present re-
view [27–30]. All of them evaluated the role of FCH PET/CT for the detec-
tion of disease relapse on the basis of biochemical recurrence after
primary treatment. Marzola et al. [27] demonstrated a detection rate
of 54% in 233 patients previously treated by radical prostatectomy,
while a slightly higher detection rate (n = 50; 64%) was obtained by
Hodolic et al. [30]. Henninger et al. [28] demonstrated a sensibility of
80% and 50% (n = 35 subjects), respectively, in relation to the concom-
itant administration of androgen deprivation treatment (ADT) and no
administration, while Oprea-Lager et al. [29] did not report any data re-
lated on sensitivity.
Finally, Schillaci et al. [31], Soyka et al. [32], Pinkawa et al. [33], and
recently Kjölhede et al. [34] and Gacci et al. [35] described the utility
of 18 F-choline in PCa patients, although they did not clearly mention
fluoride-labeled choline. Contact with each author revealed that the
source of radiopharmaceutical was FCH. Schillaci et al. [31] investigating
the relationship between PSA kinetic and PET/CT detection rate after
radical prostatectomy, found that the sensitivity of FCH PET/CT was
higher in patients with a PSA doubling time (PSAdt) of ≤ 6 months
and especially in those with a PSA velocity (PSAvel) of N2 ng/ml per
year. Kjölhede et al. [34] reported a high specificity (value = 92%) of
FCH in depicting lymph node metastases in patients with high-risk
PCa. Gacci et al. [35] established a cut-off of b6 months and N6 ng/mL/
month, respectively for PSAdt and PSAvel for the prediction of a positive
4 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx

Table 1
Characteristics of selected studies.

Authors, ref Journals, Study design N of 18 F-labeled Dosage PET Key point of literature
year patients choline and protocol
PET scanner

1 Kwee JNM, 2014 Prospective 30 FCH PET/CT 2.6 MBq/kg WBS at Metabolic metastatic indices, such as
et al., 25 12–15 min metabolic tumor activity and total lesion activity are
independently associated with a poor prognosis in
castrate resistant prostate cancer patients
2 Kjölhede World J Prospective 112 Not specified 4 MBq/kg WBS at PET/CT with radiolabeled choline has low accuracy in
et al., 34 Urol, 2014 choline PET/CTa 60–90 min excluding local lymph node dissemination of disease,
but has high performance in depicting metastasis
outside the template of an extended pelvic lymph
node dissection.
3 Buchegger EJNMMI, Prospective 23 FCH PET/CT 307 ± 16 Dyn + WBS 11C-acetate and FCH have the same sensitivity
et al., 26 2014 MBq/kg at 45 min for the detection of early recurrent PCa.
4 Gacci Scand J Urol Longitudinal 103 Not specified – Dyn + WBS PET/CT with fluorocholine is able to detect the presence
et al., 35 choline PET/CTa at 60 min of disease in case of an absolute change in PSA between
two consecutive PET scans N5 ng/mL, a PSAdt b 6 months
and a PSAvel N6 ng/mL/month
5 Afshar- EJNMMI, Retrospective 37 FCH vs. 68Ga- 3 MBq/kg WBS at 68Ga-PMSA was more sensitive than FCH PET/CT
Oromieh 2014 and PSMA PET/CT 60 min in detection of lesions even at low PSA levels.
et al., 40 comparative
6 Beheshti JNM, 2013 Prospective 250 FCH PETCT 4.07 MBq/kg Dyn + WBS Trigger PSA and ADT are the two significant predictors
et al., 19 at 10 min of FCH-positive PET lesions. ADT seems to not impair
FCH uptake in hormone-refractory prostate cancer patients.
7 Wetter Invest Prospective 15 FCH PET/MRI N.A. WBS at PET/MRI has the advantage of combining high resolution prostate
et al., 22 Radiol, 2013 150 min images, functional studies, and metabolic/molecular imaging.
8 Marzola Clin Nucl Retrospective 331 FCH PET/CT 3 MBq/kg Early pelvis The recurrence detection rate using FCH PET/CT
et al., 27 Med, 2013 static scan increased with the increase in trigger PSA value,
(5–10 min) + and even more in those patients presenting with
WBS at fast PSAdt and fast PSAvel. Moreover FCH PET/CT
60 min can detect disease relapse in more than 50% of
PCa patients with biochemical relapse and negative CI
9 Tilki European Retrospective 56 FEC PET/CT Mean dose: WBS at FEC PET/CT is not adequately accurate for the exact
et al., 14 Urology, 300 MBq 60 min localization of all metastatic lymph nodes. One third
2013 of affected lymph nodes was missed; lower
sensitivity was recorded for retroperitoneal region.
10 Poulsen BUJI, 2012 Prospective 210 FCH PET/CT 4 MBq/kg WBS at FCH PET/CT is not ideal for primary lymph node
et al., 17 60 min staging due to its low sensitivity (73.2% and 56.2%
per patient-based and per lesion-based analysis)
11 Graute EJNMMI, Prospective 82 FEC and FCH Mean dose: WBS at It is most likely to reveal disease sites when PSA level
et al., 13 2012 PET/CT 300 MBq 60 min exceeds 1.74 ng/ml after radical prostatectomy.
12 Panebianco E J Radiol, Prospective and 84 FCH PET/CT 185–259 WBS at FCH PET/CT shows low sensitivity in detection of local
et al., 39 2012 Comparative MBq 60 min recurrence when PSA value is lower than 2 ng/mL.
Conversely, DCEMR shows a higher diagnostic accuracy
also for a PSA value ranged between 0.2 and 2.0 ng/mL.
13 Henninger Nucl Med Retrospective 35 FCH PET 4 MBq/kg Dyn It is an accurate method for detection of recurrences
et al., 28 Commun, (1 min) + after radical prostatectomy in patients in
2012 WBS at ADT even at PSA value b4 ng/dL.
60 min
14 Oprea- PLOS ONE, Retrospective 25 FCH PET/CT 4 MBq/kg Dyn (after An acquisition at 30 min after iv may be a reasonable
Lager 2012 2 min) + alternative for predicting the nodal status. In particular,
et al., 29 WBS at reactive nodes remained detectable for 30 min after iv.
30 min
15 Schillaci EJNMMI, Not specified 49 Not specified 370 MBq WBS at The detection rate was directly related to the
et al., 31 2012 PET/CTa 45 min absolute PSA values; in particular, the sensitivity
of PET is higher in patients with PSAdt ≤ 6mo
and PSAvel N 2 ng/mL per year.
16 Soyka EJNMMI, Retrospective 156 Not specified 200–300 MBq Early WBS at 18 F-Choline PET/CT in patients with recurrent PCa
et al., [32] 2012 PET/CTa 3–4 min + had an important impact on therapeutic strategy and
WBS at 15– it was able to help determine an appropriate treatment
20 min in these patients.
17 Wurschmidt Radiation Prospective 26 FEC PET/CT 5 MBq/kg Dyn (after FEC PET/CT could be helpful in dose escalation in
et al., 16 Oncol, 2011 2 min) + PCa patients allowing boost dose N 60 Gy to
WBS at metastatic lymph nodal regions if PET/CT-planned
60–90 min intensity modulated and image guided radiotherapy
is used.
18 Hodolic, 30 Radiol Retrospective 50 FCH PET/CT 200–300 MBq Dyn (0–5 FCH PET/CT seems to be a useful imaging modality
Oncol, min) + WBS in patients with PCa; it can demonstrate spread
2011 at 60 min of the disease preoperatively and detect the local
recurrence after RP.
19 Steuber EJC, 2010 Prospective 20 FEC PET/CT 300–400 MBq WBS at FEC PET/CT cannot be recommended for routine clinical use
et al., 15 60 min to detect occult LN metastasis prior to initial treatment.
20 Pinkawa Strahlenther Prospective 66 Not specified 178–355 MBq WBS at Treatment planning with FCH PET/CT allows the definition of
et al., 33 Onkol, 2010 PET/CTa 60 min an integrated boost in nearly all PCa patients without
considerably increasing of equivalent uniform dose and

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx 5

Table 1 (continued)

Authors, ref Journals, Study design N of 18 F-labeled Dosage PET Key point of literature
year patients choline and protocol
PET scanner

normal-tissue complication probability.

21 McCarthy EJNMMI, Prospective 26 FCH PET and 200 MBq Early pelvis FCH PET demonstrated an overall concordance of
et al., 36 2011 PET/CT static scan 81% with BS and CT and an accuracy of 96% on
(5 min) + a lesion-based analysis. In particular, it appears to
WBS at 5 min differentiate malignant nodal involvement
from reactive change on CT images.
22 Beheshti Radiology, Prospective 130 FCH PET/CT 4.07 MBq/kg 6–7 WBSs It could be a useful one-stop diagnostic procedure
et al., 18 2010 after especially in high risk patients to exclude distant
10 min + metastases when surgical approach is planned.
late WBS
at 90–120
min
23 Poulsen BJUI, 2010 Prospective 25 FCH PET/CT 4 MBq/kg WBS at 15 The authors support the use of FCH PET/CT as a tool for
et al., 23 min + WBS lymph nodes staging in intermediate or high
at 60 min risk patients.
24 Beheshti EJNMMI, Prospective 38 FCH PET/CT vs. 4.07 MBq/kg Dyn FCH PET/CT was less sensitive than 18 F-fluoride PET/CT
et al., 37 2008 and Fluoride PET/CT (8 min) + for the detection of bone metastases. FCH has the
Comparative WBS at 8 minpotential to become a one-stop diagnostic procedure
in high risk patients in particular for early detection of
bone marrow metastases.
25 Pelosi Radiol med, Retrospective 56 FCH PET/CT 185–259 MBq WBS at It is a useful diagnostic modality in patient with
et al., 41 2008 60 min PSA N 5 ng/mL (sensitivity = 81,8%). The detection
rate is very low in patients with PSA b1 ng/mL
(sensitivity = 20%), while it increases when PSA value
is between 1 and 5 ng/mL (sensitivity = 44%).
26 Husarik EJNMMI, Prospective 111 FCH PET/CT 200 MBq WBS at 2 min It is not suitable for the initial staging of PCa due its
et al., 20 2008 low sensitivity (=20%) in detecting lymph nodes
metastases. On the contrary, it is the most accurate imaging
modality to identify the location of recurrent disease,
even though the sensitivity rate is rater moderate (=86%).
27 Vees et al., BJUI, 2007 Prospective 11 FCH PET/CT vs. 214 ± 14 MBq WBS at 2 min Even if labeled PET/CT succeeded in detecting local or
38 and 11C-Acetate recurrent disease, it cannot yet be recommended as a
Comparative PET/CT standard diagnostic tool for early relapse or suspicious
of persistent disease after surgery. It may be indicated
for high risk patients for distant relapse after
radiotherapy also at low PSA value.
28 Hacker J Urol, 2006 Prospective 20 FCH PET/CT 4.07 MBq/kg Dyn (8 min) + FCH is not useful in searching for occult lymph node
et al., 24 WBS at metastasis in clinically advanced PCa, while sentinel
8 min guided PLND allows the detection of even small lymph
node disease.
29 Cimitan EJNMMI, Prospective 100 FCH PET/CT 3.7–4.07 MBq/kg WBS at 5– FCH could be useful in patients with high PSA levels
et al., 21 2006 15 min + (N4 ng/mL) and/or poorly differentiated PCa (GS N7)
WBS at 60– to exclude distant metastases when salvage local
200 min treatment is intended.

WBS: whole-body scan; Dyn = dynamic acquisition; ADT: anti-androgen therapy; PSAdt: PSA doubling time; PSAvel: PSA velocity; CI: conventional imaging; DCEMR: dynamic contrast-
enhanced magnetic resonance imaging; BS: bone scan; CT: computed tomography; GS: gleason score.
a
Later confirmed, by a contact with the authors, to be FCH.

FCH PET/CT scan. The other two studies were about 1) the clinical im-
pact of FCH in 156 PCa patients by the administration of a questionnaire
[32] and 2) the use of FCH as guide for intensity-modulated radiothera-
py planning [33]. This latter study showed that 18 F-labeled choline has
an important impact on therapeutic strategy allowing the definition of
an integrated boost without a considerable increase of the equivalent
uniform dose and normal tissue complication.
3.3. FCH PET/CT vs. other imaging modalities
Five studies compared FCH PET/CT with other imaging modalities:
five were prospective and one retrospective. In detail, McCarthy et al.
[36], Beheshti et al. [37], Vees et al. [38] and Panebianco et al. [39] com-
pared FCH PET/CT with BS and CT, 18 F-NaF and MR spectroscopic imag-
ing, respectively; conversely, Afshar-Oromieh et al. [40] compared FCH
with Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] ( 68Ga-PSMA). In
particular, McCarthy et al. [36] concluded that FCH imaging may better
differentiate malignant nodal involvement from reactive change on CT
and that it is also useful as an adjunct to BS in equivocal cases (trauma
or degenerative change); furthermore, they demonstrated an overall
concordance for PET/CT with BS and CT. Beheshti et al. [37] showed
that FCH and 18 F-NaF PET/CT had the same sensitivity for detecting
bone metastases in PCa patients. In particular, the sensitivity, specificity
and accuracy of PET/CT in detection of bone metastasis in 38 patients
were 74%, 99% and 85% for FCH and 81%, 93% and 86% for 18 F-NaF, re-
spectively. The discordant cases (FCH positive and 18 F-NaF negative)
according to the authors were probably due to bone marrow metastases
without significant bone reaction and remodeling, suggesting therefore
that FCH PET/CT has an advantage in the early detection of medullary
bone metastases. Vees et al. [38] prospectively investigated the diagnos-
tic potential both of 11C-acetate and FCH PET/CT in the early detection of
PCa recurrence after surgery at PSA levels of b1 ng/mL. They demon-
strated a sensitivity of 60% and 66% for FCH PET/CT and 11C-acetate
PET, respectively. Recently, a similar study was conducted by Buchegger
et al. [26] that compared the sensitivity of 11C-Acetate and 18 F-choline
PET/CT, reporting a great concordance for both the radiopharmaceutical
agents in patients with early recurrence of PCa. As stated by the authors,
this finding suggests that both tracers visualize similar features of PCa
cells on either tracer integration in lipid synthesis or catabolic energy
provision. Panebianco et al. [39] compared the sensitivity of FCH PET/

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
6 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx

“Fluoromethylcholine” AND “Prostate” -

“Fluoroethylcholine” AND “Prostate
N=78

Medline research

“Fluoromethylcholine” “Fluoroethylcholine”
N=53 N=25
“Fluoromethylcholine” AND “Fluoroethylcholine” AND
“Prostate” “Prostate”
N=28 N=4

“Fluoromethylcoline” and “Fluorethylcholine” and “Prostate”

Inclusion criteria

N=29

Fluoroethyl and
No specified 18F-
Fluomethylcholine Fluoroethylcholine Fluoromethyl-
labeled choline
PET or PET/CT PET or PET/CT choline PET or
PET or PET/CT
N=20 N=3 PET/CT
N=5
N=1

Total number of patients: n=2147

setting of disease
N° patients and

staging: n=536
Restaging: n=1.611

Staging: n=338
Staging: n=20 Staging: n=178
Restaging:
Restaging: n=139 Restaging: n=308
n=1.164

Fig. 3. Flow-diagram of selected studies.

CT and proton MR imaging in early detection of local recurrence in pros-
tatic bed, recruiting 84 patients with a rise of PSA value after prostatec-
tomy. They showed that diagnostic accuracy of MR was also higher in
patients with low PSA value (ranged between 0.2 ng/mL and
2 ng/mL), while FCH PET/CT should be used only in patients with a
PSA value N 2.0 ng/mL. The paper of Afshar-Oromieh et al. [40] was
based on the comparison between 68Ga-PSMA and FCH for the detec-
tion of biochemical recurrence. To this aim, 37 male patients, undergo-
ing both FCH and 68Ga-PSMA PET/CT within a time window of 30 days,
were enrolled. 68Ga-PSMA and FCH PET/CT detected 78 lesions in 32 pa-
tients and 56 lesions in 26 patients, respectively. All lesions detected by
FCH PET/CT were also seen by 68Ga-PSMA PET/CT.
Although not a comparative study, Schillaci et al. [31] secondarily
compared the results of PET alone with those of the diagnostic full-
dose CT scan with contrast agent. PET alone was positive in 31 of 49 pa-
tients (63.3%), with identification of local and systemic relapse in four
and 27 patients, respectively. Of these 31 patients with a positive
PET scan, 14 had a negative CT scan. Therefore, the combination of
18
F-choline PET and diagnostic CT could be favorable.
3.4. Diagnostic performance, androgen deprivation therapy and PSA levels
Considering the variability in sensitivity of 18 F-labeled choline PET
or PET/CT, we made a separate analysis of available published data in re-
lation to ADT and PSA levels. No information about the variation of diag-
nostic accuracies for FEC PET and concomitant administration of
hormonal therapy was available from the retrieved literature. Both
Steuber et al. [15] and Tilki et al. [14] excluded from the enrollment all
patients who underwent ADT at the time of PET imaging. Moreover,
only one study found a higher PPV for patients undergoing FEC PET/CT
with a PSA value N 2 ng/mL (95.5% vs. 50%, respectively in case of
PSA N 2 ng/mL vs. PSA b 2 ng/mL) [14]. Cimitan et al. [21] and Beheshti
et al. [19] investigated the ability of FCH in detecting recurrence of PCa
on the basis of PSA levels. Cimitan et al. [21] reported that FCH could
be useful in patients with high PSA level (N 4 ng/mL) and/or a poorly dif-
ferentiated PCa (GS N 7). Conversely, Beheshti et al. [19] demonstrated
that FCH can provide useful information even in the case of PSA
level = 0.5 ng/mL (n = 250; sensitivity = 59.5%), especially in interme-
diate and high-risk patients and in patients who are under ADT (n =

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx
100; 85%). Husarik et al. [20] recorded a slight difference in sensitivity
according to the value of PSA and ongoing ADT. In particular, the authors
found a sensitivity of 87% at PSA levels of N 2 μg/l, of 86% in the case of
PSA N 2 μg/l without ADT and 84% at PSA N 2 μg/l and concomitant
ADT. Henninger et al. [28] found that the sensitivity of FCH PET was
higher in the ADT patient group than the group without (n = 35; 80%
vs. 50%, respectively). The detection rate of FCH during ADT was equal
to 67% in the study by Marzola et al. [27], being higher than that for
those who were not under ADT (value = 44%), while the detection
rate described by Pelosi et al. [41] was slightly lower (42,9%; n = 24/
56). The potential influence of ADT, such as LH-RH analogues or
bicalutamide in patients who undergo 11C-choline or 18 F-labeled cho-
line analogs PET/CT is still an unresolved matter in literature. Hara
et al. [42] demonstrated in cultured PCa cells that androgen depletion
markedly suppresses the uptake of labeled choline analogs in
androgen-sensitive PCa cells, suggesting a potential underestimation
of choline metabolism when imaging is performed during ADT [42].
Similar conclusions were achieved by Fuccio et al. [43]. But, the increase
in PSA levels during ADT is a marker of castration-resistance of PCa cells.
3.5. 18 F-choline analogs: patient preparation and acquisition protocol
3.5.1. Patient preparation
Schillaci et al. [31] described a detailed preparation for the execution
of 18 F-labeled choline PET scan. In particular, the authors suggested the
avoidance of foods containing high levels of choline, such as asparagus,
beans, soya, carrots, egg yolk, lamb, pig and calf liver, skimmed milk,
peanuts, peanut butter, peas, spinach, turnip and wheat products during
the week before the examination. Moreover, a fasting of 6 h before the
examination was required. Similarly, some authors suggested fasting
for 4–6 h before examination [23,27,30] or not performing FCH PET
scan in patients with blood glucose level higher than 200 ml/L [15]. Con-
versely, no information concerning the preparation of patients was re-
ported by Häcker et al. [24], Behesthi et al. [18,19], Husarik et al. [20],
Panebianco et al. [39], McCarthy et al. [36], Pelosi et al. [41] and Gacci
et al. [35]. According to Henninger et al. [28] fasting was not essential
to perform FCH PET/CT. Buchegger et al. [26] and Kjölhede et al. [34] re-
quired a fasting for at least 4 h before PET/CT images. Marzola et al. [27]
suggested a fasting of 6 h and 1-h avoidance of liquids to reduce bladder
filling before tracer injection. Kwee et al. [25] educated all patients to re-
frain from eating and drinking at least 3 h before undergoing PET.
Schillaci et al. [31] well hydrated their patients using a saline solution
by intravenous administration to reduce the pool of tracer in the kidney.
Moreover, approximately 600 ml of contrast-containing solution was
administered orally to opacify the intestinal loops. A similar approach
was described by Steuber et al. [15]. Finally, in the study by Würschmidt
et al. [16], between early and late images, to significantly reduce bladder
activity, patients received 20 mg furosemide and were instructed to
drink 1–1.5 L of water for forced diuresis.
3.5.2. Acquisition protocol
FCH PET and/or PET/CT acquisition protocols for PCa imaging were
not standardized. Most authors performed an early imaging acquisition
to avoid interference from bladder tracer accumulation. Early static or
dynamic acquisition of pelvis followed by a whole-body PET or PET/CT
acquisition was proposed as alternative to whole body scan (WBS)
alone, for optimizing the detection of distant disease. Early time points
for imaging (0–15 min post-intravenous injection) and/or delayed im-
aging time points (30, 40, 45, 60, 90–120 and 65–200 min post-
intravenous injection) were also described in some collected articles.
Details about PET protocols are listed in Table 1. As illustrated, patient
preparation and protocol acquisitions were not relative to the employed
compound, either FCH or FEC. Moreover, as clearly reported in Table 1,
in the majority of studies with FEC, a WBS after 60 min from tracer injec-
tion was made. Conversely, a huge variability was registered for FCH,
due to both the larger number of studies and the main purposes of trials.
Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
7
4. Discussion
Considering the available data in literature, FCH may be consid-
ered a compound with high performance and a very promising
tracer in patients with PCa, finding even today a primary role,
mainly in the restaging and/or the recruitment of patients under-
going salvage radiotherapy [44]. The chemical structure of FCH dif-
fers from FEC just for a single methylene group between the
nitrogen atom and the carbon bearing the fluorine atom (Fig. 2).
This chemical structure confers both an 80% decrease in uptake
for FEC in PC-3 prostate cancer cells and a reduction in CK-
mediated phosphorylation process. Recently, Takesh [45] de-
scribed the kinetic modeling of FCH PET/CT in PCa, reporting
that choline transport (K1) is more important than phosphoryla-
tion (K3) and that it can be considered the key factor for choline
uptake. Therefore, with both K1 and K3 being higher for FCH than
FEC, vascularity and the function of CK are better evaluated by
FCH. This latter concept could have both therapeutical and
prognostical consequences. From the analysis of collected data, it
emerged that FCH PET/CT is widely used in different countries
(n = 1502/1932; 78%), although a great variability in PET proto-
cols and in patient preparation can be identified. In some studies,
a fasting of at least 4 h, a diet including food with low levels of cho-
line the week before the scan, or defined hydrating conditions are
required, although no data about the effects of food and hydration
on the biodistribution of the radiolabeled choline are currently
available. Also, PET protocol represents an important limitation
for a rigorous comparison between different studies. Acquisition
times may vary. In the studies examined, we found: dynamic
image from 1 to 8 min after injection of tracer, a very early WBS
(after 8 min), moderately early WBS (after 30 min), a conventional
WBS (after 60 min) or late WBS (after 120 min). The variability of
PET image acquisition can alter the diagnostic performance of the
examination and of the employed radiopharmaceutical agents. In
fact, variations in the lesion/background ratio may be observed as
consequence of the variability of many issues, dependent either
on the subject or on the radiocompound (FCH versus FEC). For ex-
ample, a different diagnostic accuracy could be connected with no
standardized examinations, no consideration in optimizing the
scan time to obtain the best lesion/background ratio, parameters
such as temporal biodistribution of radiocholine, intracellular me-
tabolism and catabolic rate, formation and kinetics of dissimilar ra-
diochemical forms, and time and speed of filling of the bladder. In
accordance with Kwee et al. [25], volumetric measurements of
tumor choline activity are strong predictors of prognosis in meta-
static PCa. Therefore, a well-defined and complete standardization
in methodology, including patient acceptance criteria, dosing and
imaging protocols, is mandatory for a more reliable evaluation of
diagnostic accuracy in the clinical routine. Moreover, the setup of
quantitative analysis, which also gives relevance to the informa-
tion acquired by CT, could further improve the diagnostic accuracy,
trying to decrease the number of false negatives, without increas-
ing false positive results. To optimize both methodology and the
quantitative approach, an important contribution could be achieved
through a better understanding of in vivo pharmacokinetics in humans.
In fact, there is a very high rate of metabolism in vivo producing betaine;
therefore any analysis of 18 F rather than the chemical compound might
overestimate the amount of phosphocholine produced [46]. To date,
clinical reports have not yet been published that include the analysis
of catabolites and/or of other in vivo produced fluorinated radiochemi-
cal forms. An experimental study, which also analyzes metabolites,
preferably conducted in collaboration with a radiopharmacologist and
a mathematician rather than with a clinician alone, could give a relevant
contribution in defining a more rigorous diagnostic methodology.
Furthermore, the achievement of more precise data for a prognostic
stratification and/or an earlier and more effective evaluation of therapy
8 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx

Table 2
The diagnostic performances in similar studies with FCH and FEC.

FEC FCH

Authors, ref Setting, n. pts Sens. Spec. Acc. Authors, ref Setting, n. pts Sens. Spec. Acc.

Tilki et al., 14b Restaging, 56 68.4% 73.3% 70.2% Pelosi et al., 41a Restaging, 56 82.7% 96.2% 89.2%
Wurschmidt et al.a, 16 Restaging, 26 92.3% – – McCarthy et al., 36b Restaging, 26 96% 96% 96%
Steuber et al., 15a Staging, 20 0% 100% – Poulsen et al., 23a Staging, 25 100% 95% 96%
a
Patient-based analysis.
b
Lesion-based analysis.

response could be obtained. Few data about the differences between
FCH and FEC, from a clinical point of view, are now available. From the
analysis of the reports, it emerged that the diagnostic performances of
FCH and FEC for the detection of lymph node metastasis before a surgi-
cal approach are generally low, with values typically around 50% or less
for FCH and between 0% and 39% for FEC. Conversely, either of the
tracers appears useful for the detection of recurrent PCa, in the case of
increase in absolute PSA value or in the case of high levels of PSAvel
and PSAdt (sensitivity ranged between 42.9% and 96% for FCH and be-
tween 62% and 85.7% for FEC). Table 2 reports the diagnostic perfor-
mances in similar studies with FCH and FEC.
To date, it is not possible to determine whether FCH is superior to
FEC, or vice versa. The discrepancy between the number of studies
based on FCH and those based on FEC is very important, with the num-
ber of FEC reports being very small (n = 3 versus n = 20, respectively
for FEC and FCH). This limitation could affect the conclusions and our
considerations. Nevertheless, from a comparison between similar stud-
ies involving a comparable number of patients and in the same setting
of disease (see Table 2), it appears that FCH has a higher diagnostic per-
formance than FEC, particularly for recurrence detection. Probably, this
latter advantage could be linked with less uptake in the bowel of FCH as
compared to FEC, which could reduce the detection of abdominal lymph
nodes [47]. Furthermore, it has to be pointed out that Graute et al. [13],
in their comparative study between FCH and FEC, conclude with the fol-
lowing sentence: “In fact, no systematic comparison (between FEC and
FCH) has yet been made in vivo, but FCH may have slightly superior
properties in vitro” [48].
4.1. Implication for practice
On the basis of our experience, also directed by the careful evaluation
of the literature, we suggest different protocols in accordance to the re-
quests of the oncologists, urologists or radiotherapists. Firstly, the patients
should be advised to fast for a minimum of 6-h before the examination, to
be well-hydrated and to void the bladder before the tracer injection and/
FEC and FCH PET
protocols in prostate
cancer patients
or PET examination. Secondly, in order to reduce the bowel uptake and a
competitive uptake, patients should be invited in the 24 h before the scan
to drink at least 1.5-2 l of water (or other fluids) and to avoid food con-
taining choline (such as such as asparagus, beans, soya, carrots, egg
yolk, lamb, pig and calf liver, skimmed milk, peanuts, peanut butter,
peas, spinach, turnip and wheat products, as suggested by Schillaci et al.
[31]). The acquisition protocol should be based on the clinical request.
In particular, in the case of suspicious for prostatic fossae recurrence, a dy-
namic imaging (for at least 8 min from the injection of tracer) or a very
early static imaging (maximum 2 min after the injection) with a duration
of 5 min may be helpful. In case of suspicious for lymph node involve-
ment, a late whole-body imaging is suggested (at least 30–60 min after
injection; 3–4 min/bed). Finally, if distant skeletal and/or visceral metas-
tases are suspected, a delayed whole-body scan (after 60 min from the in-
jection; 3–4 min/bed) should be performed. In our experience, a delayed
whole-body scan (after 60 min from the tracer injection) alone is recom-
mended to increase the detection rate of PET/CT with FCH or FEC, for
lymph node and distant organs involvement. A summary of a suggested
protocol is shown in Fig. 4.
5. Conclusion
In our opinion, FCH is already recruited in the toolbox for diagnosis
of recurrence in patients with PCa. FCH seems to be a more appropriate
radiopharmaceutical agent compared to FEC, although more compara-
tive data are mandatory. The variability on patient preparation, imaging
acquisition and the clinical setting makes it difficult to make a final de-
cision. A well designed and prospective trial for the evaluation of
biokinetic data and diagnostic performance of both radiopharmaceuti-
cal agents seems essential, because nowadays we are not able to deter-
mine the difference in clinical practice between FEC and FCH linked to
the different chemical features. It will also be interesting to see how
all PCa imaging agents fit into the current clinical standard of practice,
which probably still contains 99Tc-MDP, subsequently substituted by
18
F-NaF. In the near future, radiolabeled PSMA radiotracers, which
have already aroused great clinical interest in preliminary studies, will
also be added to 18 F and 11C radiolabeled-choline agents.
Conflict of interest

Nothing to declare.

Prostatic fossae Lymph nodes Distant organs Appendix A. Supplementary data

Supplementary data to this article can be found online at http://dx.

doi.org/10.1016/j.nucmedbio.2014.12.019.
• Dynamic imaging
(for 8 minutes) References
Delayed whole-body scan (after 30-60 minutes from
• Early static scan the injection)
(after 2 minutes [1] Mertens K, Slaets D, Lambert B, Acou M, De Vos F, Goethals I. PET with (18)F-labelled
from injection) choline-based tracers for tumour imaging: a review of the literature. Eur J Nucl Med
Mol Imaging 2010;37:2188–93.
[2] Hara T, Bansal A, DeGrado TR. Choline transporter as a novel target for molecular im-
Fig. 4. A schematic summary of 18 F-FCH PET or PET/CT protocol. aging of cancer. Mol Imaging 2006;5:498–509.

Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
 L. Evangelista et al. / Nuclear Medicine and Biology xxx (2015) xxx–xxx
[3] Ramírez de Molina A, Rodriguez-Gonzalez A, Gutiérrez R, Martínez-Piñeiro L,
Sánchez J, Bonilla F, et al. Overexpression of choline kinase is a frequent feature in
human tumor-derived cell lines and in lung, prostate, and colorectal human cancers.
Biochem Biophys Res Commun 2002;296:580–3.
[4] Yoshimoto M, Watanabe IS, Martins MT, Salles MB, Ten Eyck GR, Coelho PG. Micro-
structural and ultrastructural assessment of inferior alveolar nerve damage follow-
ing nerve lateralization and implant placement: an experimental study in rabbits.
Int J Oral Maxillofac Implants 2009;24:859–65.
[5] Cho SY, Szabo Z. Molecular imaging of urogenital diseases. Semin Nucl Med 2014;
44:93–109.
[6] Authors NL. FDA approves 11C-choline for PET in prostate cancer. J Nucl Med 2012;
53:11N.
[7] Tuncel M, Souvatzoglou M, Herrmann K, Stollfuss J, Schuster T, Weirich G, et al.
[(11)C]Choline positron emission tomography/computed tomography for staging and
restaging of patients with advanced prostate cancer. Nucl Med Biol 2008;35:689–95.
[8] Castellucci P, Fuccio C, Rubello D, Schiavina R, Santi I, Nanni C, et al. Is there a role for
11C-choline PET/CT in the early detection of metastatic disease in surgically treated
prostate cancer patients with a mild PSA increase b1.5 ng/ml? Eur J Nucl Med Mol
Imaging 2011;38:55–63.
[9] Hara T, Yamamoto M. Automated synthesis of fluorine-18 labeled choline analogue: 2-
fluoroethyl-dimethyl-2-oxyethylammonium. J Nucl Med 1997;38:44P [abstract, suppl].
[10] Hara T, Kosala N, Kishi H. Development of (18)F-fluoroethylcholine for cancer imag-
ing with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med
2002;43:187–99.
[11] DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN, et al. Synthe-
sis and evaluation of 18 F-labeled choline as an oncologic tracer for positron emis-
sion tomography: initial findings in prostate cancer. Cancer Res 2001;61:110–7.
[12] Uusijärvi H, Nilsson LE, Bjartell A, Mattsson S. Biokinetics of 18 F-choline studied in
four prostate cancer patients. Radiat Prot Dosimetry 2010;139:240–4.
[13] Graute V, Jansen N, Ubleis C, Seitz M, Hartenbach M, Scherr MK, et al. Relationship
between PSA kinetics and (18 F)fluorocholine PET/CT detection rates of recurrence
in patients with prostate cancer after total prostatectomy. Eur J Nucl Med Mol Imag-
ing 2012;39:271–82.
[14] Tilki D, Reich O, Graser A, Hacker M, Silchinger J, Becker AJ, et al. 18 F-
Fluoroethylcholine PET/CT identifies lymph node metastasis in patients with
prostate-specific antigen failure after radical prostatectomy but underestimates its
extent. Eur Urol 2013;63:792–6.
[15] Steuber T, Schlomm T, Heinzer H, Zacharias M, Ahyai S, Chun KF, et al. [F(18)]-
fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node me-
tastasis in high risk prostate cancer patients prior to radical prostatectomy: prelim-
inary results from a prospective histology-based study. Eur J Cancer 2010;46:
449–55.
[16] Würschmidt F, Petersen C, Wahl A, Dahle J, Kretschmer M. [18F]fluoroethylcholine-
PET/CT imaging for radiation treatment planning of recurrent and primary prostate
cancer with dose escalation to PET/CT-positive lymph nodes. Radiat Oncol 2011;6:
1–8 [44].
[17] Poulsen MH, Bouchelouche K, Høilund-Carlsen PF, Petersen H, Gerke O, Steffansen
SI, et al. [18 F]fluoromethylcholine (FCH) positron emission tomography/computed
tomography (PET/CT) for lymph node staging of prostate cancer: a prospective
study of 210 patients. BJU Int 2012;110:1666–71.
[18] Beheshti M, Imamovic L, Broinger G, Vali R, Waldenberger P, Stoiber F, et al. 18 F
choline PET/CT in the preoperative staging of prostate cancer in patients with inter-
mediate or high risk of extracapsular disease: a prospective study of 130 patients.
Radiology 2010;254:925–33.
[19] Beheshti M, Haim S, Zakavi R, Steinmair M, Waldenberger P, Kunit T, et al. Impact of
18 F-choline PET/CT in prostate cancer patients with biochemical recurrence: influ-
ence of androgen deprivation therapy and correlation with PSA kinetics. J Nucl Med
2013;54:833–40.
[20] Husarik DB, Miralbell R, Dubs M, John H, Giger OT, Gelet A, et al. Evaluation of
(18 F)-choline PET/CT for staging and restaging of prostate cancer. Eur J Nucl Med
Mol Imaging 2008;35:253–63.
[21] Cimitan M, Bortoluss R, Morassut S, Canzonieri V, Garbeglio A, Baresic T, et al.
(18 F)fluorocholine PET/CT imaging for the detection of recurrent cancer at PSA relapse:
experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging 2006;33:1387–98.
[22] Wetter A, Lipponer C, Nensa F, Beiderwellen K, Olbricht T, Rübben H, et al. Simulta-
neous 18 F choline positron emission tomography/magnetic resonance imaging of
the prostate: initial results. Invest Radiol 2013;48:256–62.
[23] Poulsen MH, Bouchelouche K, Gerke O, Petersen H, Svolgaard B, Marcussen N, et al.
[18 F]-fluorocholine positron-emission/computed tomography for lymph node stag-
ing of patients with prostate cancer: preliminary results of a prospective study. BJU
Int 2010;106:639–43.
[24] Häcker A, Jeschke S, Leeb K, Prammer K, Ziegerhofer J, Sega W, et al. Detection of pel-
vic lymph node metastases in patients with clinically localized prostate cancer: com-
parison of [18 F]fluorocholine positron emission tomography-computerized
tomography and laparoscopic radioisotope guided sentinel lymph node dissection.
J Urol 2006;176:2014–9.
[25] Kwee SA, Lim J, Watanabe A, Kromer-Baker K, Coel MN. Prognosis related to meta-
static burden measured by 18 F-fluorocholine PET/CT in castration-resistant prostate
cancer. J Nucl Med 2014;55:905–10.
Please cite this article as: Evangelista L., et al, 18F-fluorometilcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A
literature revision, Nucl Med Biol (2015), http://dx.doi.org/10.1016/j.nucmedbio.2014.12.019
9
[26] Buchegger F, Garibotto V, Zilli T, Allainmant L, Jorcano S, Vees H, et al. First imaging
results of an intraindividual comparison of 11C-acetate and 18 F-fluorocholine PET/
CT in patients with prostate cancer at early biochemical first or second relapse after
prostatectomy or radiotherapy. Eur J Nucl Med Mol Imaging 2014;41:68–78.
[27] Marzola MC, Chondrogiannis S, Ferretti A, Grassetto G, Rampin L, Massaro A, et al.
Role of 18 F-choline PET/CT in biochemically relpased prostate cancer after radical
prostatectomy. Clin Nucl Med 2013;38:e26–32.
[28] Henninger B, Vesco P, Putzer D, Kendler D, Loizides A, Bale RJ. (18 F)choline positron
emission tomography in prostate cancer patients with biochemical recurrence after
radical prostatectomy: influence of antiandrogen therapy — a preliminary study.
Nucl Med Commun 2012;33:889–94.
[29] Oprea-Lager DE, Vincent AD, van Moorselaar RJ, Gerritsen WR, van den Eertwegh AJ,
Eriksson J, et al. Dual-phase PET-CT to differentiate [18 F]Fluoromethylcholine up-
take in reactive and malignant lymph nodes in patients with prostate cancer. PLoS
One 2012;7:1–9 [e48430].
[30] Hodolic M. Role of 18 F-choline PET/CT in evaluation of patients with prostate carci-
noma. Radiol Oncol 2011;45:17–21.
[31] Schillaci O, Calabria F, Tavolozza M, Ragano Caracciolo C, Finazzi Agrò E, Miano R,
et al. Influence of PSA, PSA velocity and PSA doubling time on contrast-enhanced
18 F-choline PET/CT detection rate in patients with rising PSA after radical prostatec-
tomy. Eur J Nucl Med Mol Imaging 2012;39:589–96.
[32] Soyka JD, Muster MA, Schmid DT, Seifert B, Schick U, Miralbell R, et al. Clinical impact
of 18 F-choline PET/CT in patients with recurrent prostate cancer. Eur J Nucl Med
Mol Imaging 2012;39:936–43.
[33] Pinkawa M, Holy R, Piroth MD, Klotz J, Nussen S, Krohn T, et al. Intensity-modulated
radiotherapy for prostate cancer implementing molecular imaging with 18 F-choline
PET-CT to define a simultaneous integrated boost. Strahlenther Onkol 2010;186:
600–6.
[34] Kjolhede H, Ahlgren G, Almquist H, Liedberg F, Lyttkens K, Ohlsson T, et al. 18 F-
fluorocholine PET/CT compared with extended pelvic lymph node dissection in
high-risk prostate cancer. World J Urol 2014;32:965–70.
[35] Gacci M, Cai T, Siena G, Minervini A, Torshizi MF, Bartolini M, et al. Prostate-specific
antigen kinetics parameters are predictive of positron emission tomography fea-
tures worsening in patients with biochemical relapse after prostate cancer treat-
ment with radical intent: results from a longitudinal cohort study. Scand J Urol
2014;48:259–67.
[36] McCarthy M, Slew T, Campbell A, Lenzo N, Spry N, Vivian J, et al. 18 F-
Fluoromethylcholine (FCH) PET imaging in patients with castration-resistant pros-
tate cancer: prospective comparison with standard imaging. Eur J Nucl Med Mol Im-
aging 2011;38:14–22.
[37] Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Loidl W, et al. Detection of bone
metastases in patients with prostate cancer by 18 F fluorocholine and 18 F fluoride
PET-CT: a comparative study. Eur J Nucl Med Mol Imaging 2008;35:1766–74.
[38] Vees H, Buchegger F, Albrech S, Khan H, Husarik D, Zaidi H, et al. 18 F-choline and
11C-acetate positron emission tomography: detection of residual or progressive
subclinical disease at very low prostate specific antigen values (b1 ng/mL) after rad-
ical prostatectomy. BJU Int 2007;99:1415–20.
[39] Panebianco V, Sciarra A, Lisi D, Galati F, Buonocore V, Catalano C, et al. Prostate can-
cer: 1HMRS-DCEMR at 3 T versus (18 F)choline PET/CT in the detection of local
prostate cancer recurrence in men with biochemical progression after radical
retropubic prostatectomy (RRP). Eur J Radiol 2012;81:700–8.
[40] Afshar-Oromieh A, Haberkorn U, Schlemmer HP, Fenchel M, Eder M, Eisenhut M,
et al. Comparison of PET/CT and PET/MRI hybrid systems using a (68)Ga-labelled
PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur
J Nucl Med Mol Imaging 2014;41:887–97.
[41] Pelosi E, Arena V, Skanjeti A, Pirro V, Douroukas A, Pupi A, et al. Role of whole-body
18 F-choline PET/CT in disease detection in patients with biochemical relapse after
radical treatment for prostate cancer. Radiol Med 2008;113:895–904.
[42] Hara T, Bansal A, DeGrado TR. Effect of hypoxia on the uptake of [methyl-3H]choline,
[1-14C] acetate and [18 F]FDG in cultured prostate cancer cells. Nucl Med Biol 2006;
33:977–84.
[43] Fuccio C, Schiavina R, Castellucci P, Rubello D, Martorana G, Celli M, et al. Androgen
deprivation therapy influences the uptake of 11C-choline in patients with recurrent
prostate cancer: the preliminary results of a sequential PET/CT study. Eur J Nucl Med
Mol Imaging 2011;38:1985–9.
[44] Mansi L, Cuccurullo V, Evangelista L. Is radiocholine PET/CT already clinically useful
in patients with prostate cancer? J Nucl Med 2014;55:1401–3.
[45] Takesh M. Kinetic modeling application to 18 F-fluoroethylcholine positron emission
tomography in patients with primary and recurrent prostate cancer using two-
tissue compartmental model. World J Nucl Med 2013;12:101–10.
[46] Witney TH, Alam IS, Turton DR, Smith G, Carroll L, Brickute D, et al. Evaluation of
deuterated 18 F- and 11C-labeled choline analogs for cancer detection by positron
emission tomography. Clin Cancer Res 2012;18:1063–72.
[47] Filice A, Asti M, Roncali M, Fraternali A, Casali M, Di Paolo M, et al. Comparison be-
tween the physiological distribution of 18 F-FMCH and 18 F-FECH. Eur J Nucl Med
Mol Imaging Suppl 2010;37:P466 [abstract, suppl].
[48] DeGrado TR, Baldwin SW, Wang S, Orr MD, Liao RP, Friedman HS, et al. Synthesis
and evaluation of 18 F-labeled choline analogs as oncologic PET tracers. J Nucl
Med 2001;42:1805–14.