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Use of pinhole dual-phase Tc-99m sestamibi vs combined Tc-99m sestamibi

and Tc-99m pertechnetate scintigraphy in patients with hyperparathyroidism
where single-photon emission comp...

Article  in  Nuclear Medicine Communications · December 2019

DOI: 10.1097/MNM.0000000000001124

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Original article
Use of pinhole dual-phase Tc-99m sestamibi vs combined
Tc-99m sestamibi and Tc-99m pertechnetate scintigraphy
in patients with hyperparathyroidism where single-photon
emission computed tomography/computed tomography is
unavailable
Malik Eid Juweida, Yanal Omaria, Nahla Khawajab, Abedallatif AlSharifa,
Suhad Al-Monyerb, Sara Jwaieda, Liza Shabana, Cathrina Lahama,
Eyad Alajlonya, Ahmad Karkasha and Kamel Ajlounib
Objective  To compare the sensitivity and positive
predictive value (PPV) of pinhole dual-phase Tc-99m
sestamibi vs combined Tc-99m sestamibi and
Tc-99m pertechnetate scintigraphy in patients with
hyperparathyroidism where single-photon emission
computed tomography (SPECT)/CT is unavailable.
Methods  All patients with biochemically proven
hyperparathyroidism who underwent both pinhole
Tc-99m sestamibi and Tc-99m pertechnetate scintigraphy
between January 2012 and December 2017 with surgery
performed within 3 months of imaging were analyzed.
Tc-99m sestamibi images alone and combined with
Tc-99m pertechnetate images were interpreted by two
nuclear medicine physicians. The sensitivity and PPV of
the two imaging approaches were determined based on
the surgical findings.
Results  Of the 38 patients included, surgery revealed
33 single parathyroid adenomas (PA), one double
adenoma and four parathyroid hyperplasia (PH). On a
per-patient basis, the sensitivity and PPV for detection of
PA or PH were 76% and 100%, respectively, with Tc-99m
sestamibi alone vs 84% and 100% using the combined
approach. For PA, the sensitivity and PPV were 82% and
100%, respectively, with Tc-99m sestamibi alone vs. 91%
Introduction
Parathyroid scintigraphy using technetium-99m sesta-
mibi (Tc-99m MIBI) is a well established approach for
localizing parathyroid adenoma and hyperplasia, par-
ticularly in the setting of primary hyperparathyroidism
[1–27]. However, the Tc-99m MIBI-based imaging proto-
cols vary widely [4–27]. In some protocols, Tc-99m MIBI
is used alone with images obtained at early and delayed
timepoints (dual-phase approach), while in others, Tc-
99m MIBI is combined with I-123 or Technetium-99m
pertechnetate (Tc-99m pertechnetate) thyroid scintigra-
phy, an approach termed ‘dual-tracer’ [1–27]. The dual-
tracer approach is particularly useful when it is unclear
whether the abnormality seen on the Tc-99m MIBI scan
0143-3636 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
and 100% with the combined approach. PH was identified
in only one of four patients with Tc-99m sestamibi alone
or in combination. There were no significant differences in
sensitivity (P = 0.08) and PPV (P > 0.99) between Tc-99m
sestamibi alone and Tc-99m sestamibi with Tc-99m
pertechnetate.
Conclusion  Pinhole dual-phase Tc-99m sestamibi
alone has high accuracy in the detection of PA. The routine
addition of Tc-99m pertechnetate to Tc-99m sestamibi
does not result in significant improvement in the detection
of PA or PH and should be reserved for equivocal cases.
Nucl Med Commun XXX:000–000 Copyright © 2019
Wolters Kluwer Health, Inc. All rights reserved.
Nuclear Medicine Communications 2019, XXX:000–000
Keywords: pinhole collimator, parathyroid scintigraphy, Tc-99m MIBI,
Tc-99m pertechnetate, thyroid scintigraphy
a
Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine
and  bThe National Center (Institute) for Diabetes, Endocrinology and Genetics,
University of Jordan, Amman, Jordan
Correspondence to Malik Eid Juweid, MD, Department of Radiology and Nuclear
Medicine University of Jordan Hospital, Queen Rania Street Al Jubeiha, Amman
11942, Jordan
Tel: +962 798515972; fax: +962 65353388; e-mail: mjuweid@yahoo.com
Received 21 July 2019 Accepted 31 October 2019
is thyroidal or parathyroidal in origin and has been shown
to increase the accuracy of parathyroid scintigraphy
[6,8–10,13]. In addition, there is variability in the type of
collimation used for planar acquisition (parallel-hole vs
pinhole collimation) with several studies demonstrating
the superiority of the latter [11–13]. Yet, many institu-
tions use planar software zoom, single-photon emission
computed tomography (SPECT) and, more recently,
SPECT/CT in an effort to increase the accuracy of this
imaging approach [5–7,14–23,26,27].
At our institution, we routinely perform dual-phase
Tc-99m MIBI pinhole planar  parathyroid scintigra-
phy, termed herein MIBI-PPS followed by Tc-99m
DOI: 10.1097/MNM.0000000000001124
2  Nuclear Medicine Communications  2019, Vol XXX No XXX
pertechnetate pinhole  planar thyroid scintigraphy
(PPTS) after the delayed Tc-99m MIBI image. In addi-
tion, we always acquire an early Tc-99m MIBI image of
the thorax (using a high-resolution parallel-hole collima-
tor) to detect any ectopic mediastinal or thoracic para-
thyroid adenomas. Pinhole imaging is used because a
SPECT/CT device is unavailable at our institution and
because MIBI-PPS has been reported to be superior to
MIBI parallel-hole planar parathyroid scintigraphy [11–
13], and at least as sensitive as SPECT for detection of
parathyroid abnormalities [5,8,11–13,15,24,25], with one
head-to-head comparison showing that pinhole imaging
was superior to SPECT in parathyroid adenoma detec-
tion [16].
The objective of the current investigation is to compare
the sensitivity and positive predictive value (PPV) of
MIBI-PPS vs combined MIBI-PPS and PPTS in patients
with hyperparathyroidism where SPECT/CT is unavail-
able. This comparison was undertaken in hyperparathy-
roid patients who underwent parathyroid surgery as the
reference standard in order to determine whether PPTS
should be routinely performed together with MIBI-PPS.
Patients and methods
Patients
This retrospective study was approved by the relevant
institutional review board. The study cohort included all
patients with biochemically proven hyperparathyroidism
who underwent both MIBI-PPS and PPTS between 1
January 2012 and 31 December 2017 with surgery per-
formed within 3 months of imaging.
Imaging protocol
Each patient was initially administered 555 MBq (15mCi)
of Tc-99m MIBI with planar imaging of the neck per-
formed at 20 minutes and at 2–3 hours postinjection using
either a dual-head gamma camera (E.CAM; Siemens
Medical Solutions, Malvern, Pennsylvania, USA) or a
single head gamma camera (Meridian, Philips, USA)
equipped with a low-energy pinhole collimator with the
peak energy set at 140 keV with a 20% window width. In
addition, an image of the chest down to the pericardium
was acquired at 15 minutes postinjection using the same
gamma cameras but, this time using a high-resolution,
parallel-hole collimator, again with the peak energy set at
140 keV with a 20% window width.
Either immediately following the delayed (2–3 hours)
Tc-99m MIBI images or on a separate day, each patient
was also given Tc-99m pertechnetate with pinhole imag-
ing of the neck performed 20–30 minutes thereafter
using the same cameras described above with a 20% win-
dow set around the 140-keV photopeak. When given the
same day as the Tc-99m MIBI, the Tc-99m pertechnetate
injected activity was 370MBq (10 mCi) in order to over-
whelm the remaining activity from the delayed Tc-99m
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
MIBI scan. When 99mTc-pertechnetate was given on a
different day, activity was only 185 MBq (5mCi).
Image interpretation
An imaging set consisting of MIBI-PPS alone was first
retrospectively and independently interpreted by two
experienced board-certified nuclear medicine physicians
blinded to surgical outcome. In the case of disagreement,
a third blinded board-certified nuclear medicine physi-
cian served as adjudicator.
Using MIBI-PPS alone, a positive scan for parathyroid
adenoma was defined as one showing a persistent focus
of increased uptake on both the early and delayed Tc99m
MIBI images or focal uptake only apparent on the delayed
Tc99m MIBI image. Focal uptake could be seen at the
typical location of the parathyroid/thyroid glands or out-
side the parathyroid/thyroid regions (ectopic adenomas).
A positive scan for parathyroid hyperplasia was defined
as one showing two or more foci of increased uptake at
the typical location of the parathyroid glands. This liberal
definition for positivity of parathyroid hyperplasia has
been shown to increase the sensitivity for detecting par-
athyroid hyperplasia compared with requiring visualiza-
tion of all abnormal parathyroid glands [7,27]. While this
definition does not distinguish between the entities of
two adenomas and parathyroid hyperplasia, the entity of
two adenomas as a cause of hyperparathyroidism is quite
uncommon (2–3%) [7].
At least two weeks after the interpretation of the MIBI-
PPS images alone, the same two experienced nuclear
medicine physicians were presented with an imaging set
combining MIBI-PPS with PPTS for interpretation in a
blinded and independent fashion. In the case of disagree-
ment, the same blinded third nuclear medicine physician
served as adjudicator. Tc-99m pertechnetate subtraction
imaging was not used in the interpretation of the com-
bined imaging sets.
Using the combination of MIBI-PPS with PPTS, a pos-
itive scan for parathyroid adenoma was defined as one
showing a focus of increased uptake on both the early
and delayed Tc-99m MIBI images or focal uptake only
apparent on the delayed Tc-99m MIBI image provided
that the focus, in both cases is not seen on the PPTS
image (i.e., is not thyroidal in origin). However, another
definition of a positive finding was a focus of increased
uptake on the early Tc-99m MIBI image which washes
out partially or completely on the delayed Tc-99m MIBI
image but is not seen on the PPTS image, the known
entity of rapid-washout parathyroid adenoma [28–30].
The definition of parathyroid hyperplasia using the com-
bined imaging approach was similar to that using MIBI-
PPS alone in that two or more foci deemed to represent
abnormal parathyroid glands were considered indicative
of parathyroid hyperplasia provided these foci were not
present on the accompanying thyroid scan.
 Tc-99m MIBI pinhole parathyroid scintigraphy Juweid et al.  3

Statistical analysis MIBI parathyroid scintigraphy. Thirty-three patients

The McNemar test was used to compare sensitivities of
the two parathyroid imaging approaches, while the PPVs
were compared using a generalized score statistic as pro-
posed by Leisenring et al [31]. Student t-test was used
to compare the mean weights of the false-negative and
true-positive parathyroid lesions. Statistical significance
was determined at two-sided P value ≤0.05. Analyses were
performed in R version 3.5.0 and relevant packages [32].
Results
The database query for the time period between 1
January 2012 and 31 December 2017 yielded 38 patients
with biochemically proven hyperparathyroidism who
underwent both MIBI-PPS and PPTS and had parathy-
roid surgery within 3 months of imaging. Table 1 shows
the demographic and clinical characteristics of these
patients. Mean age of the patients was 54.9 years (SD;
9.9), 74% were female, 90% had primary, 5% secondary
and 5% tertiary hyperparathyroidism. Two patients (5%)
had prior parathyroid surgery.
Surgical findings
Surgery was unilateral neck exploration in 33 and bilat-
eral neck exploration in five patients, depending on the
findings of preoperative imaging, principally Tc-99m
Table 1  Patients' demographic and clinical characteristics
(n = 38)
Variables
a
Age (year)
Female, n (%)
Primary hyperparathyroidism, n (%)
Secondary hyperparathyroidism, n (%)
Tertiary hyperparathyroidism, n (%)
Prior parathyroid surgery, n (%)
Parathyroid hormone levela
Serum calcium levela
Serum phosphorus levela
a
Mean ± SD.
were found to have a single parathyroid adenoma, one
a double adenoma and four parathyroid hyperplasia.
Following their resection, calcium levels normalized in
all patients. Of the total of 35 adenomas detected in 34
patients, only two were ectopic (both located in the left
lower neck). The four patients with parathyroid hyperpla-
sia had a total of 12 hyperplastic glands. One patient had
four, two 3 and one 2 hyperplastic glands. The mean (±
SD) weight (in g) of all parathyroid lesions was 1.49 ± 2.17
(range; 0.1–13.2) with a mean weight of 1.86 ± 2.5 (range;
0.2–13.2) for the parathyroid adenomas vs 0.7 ± 0.5 for the
hyperplastic glands (range; 0.1–1.7).
Imaging findings
The MIBI-PPS scans alone were interpreted as positive
for parathyroid adenoma or parathyroid hyperplasia by
concordant readings of two nuclear medicine physicians
in 29 of the 38 patients and as negative in nine patients.
The combined MIBI-PPS and PPTS scans were inter-
preted as positive in 32 patients and negative in six
patients.
Table 2 shows the imaging findings for MIBI-PPS based
on the surgical results for all patients, those with parathy-
roid adenoma and parathyroid hyperplasia. Table 3 shows
the findings using MIBI-PPS combined with PPTS.
For parathyroid adenomas using MIBI-PPS alone or
MIBI-PPS+PPTS, a true-positive finding required that
the focal uptake on the scan correspond exactly to the
anatomical location of parathyroid adenoma at surgery,
55 ± 9.9
whereas false-positive finding was when the scan showed
28 (74%) focal uptake indicative of parathyroid adenoma with
either no surgical evidence of parathyroid adenoma or
34 (90%)
2 (5%) with a parathyroid adenoma at a location not correspond-
2 (5%) ing to the scan finding. A true-negative finding was when
2 (5%)
the scan was completely negative and no parathyroid
502 ± 793 abnormality was found at surgery, whereas a false-nega-
10.9 ± 0.9 tive finding was when the scan was negative despite the
2.9 ± 1.1
surgical presence of a parathyroid adenoma.

Table 2  Imaging findings using Tc-99 MIBI pinhole parathyroid scintigraphy in all patients, those with parathyroid adenoma and parathy-
roid hyperplasia
True positive False positive True negative False negative Sensitivity (%) PPV (%)

All patients (n = 38) 29 0 0 9 76 100

Patients with parathyroid adenoma (n = 34) 28 0 0 6 82 100
Patients with parathyroid hyperplasia (n = 4) 1 0 0 3 25 100

PPV, positive predictive value.

Table 3  Imaging findings using Tc-99 MIBI sestamibi pinhole parathyroid scintigraphy combined with Tc-99m pertechnetate pinhole
thyroid scintigraphy in all patients, those with parathyroid adenoma and parathyroid hyperplasia
True positive False positive True negative False negative Sensitivity (%) PPV (%)

All patients (n = 38) 32 0 0 6 84 100

Patients with parathyroid adenoma (n = 34) 31 0 0 3 91 100
Patients with parathyroid hyperplasia (n = 4) 1 0 0 3 25 100

PPV, positive predictive value.

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
4  Nuclear Medicine Communications  2019, Vol XXX No XXX
On a per-patient basis, the sensitivity for detection of
parathyroid adenoma or parathyroid hyperplasia for
MIBI-PPS was 76% (29/38); 82% (28/34) for parathyroid
adenoma and 25% (1/4) for parathyroid hyperplasia. The
PPV for detection of parathyroid adenoma or parathyroid
hyperplasia was 100% (29/29); 28/28 for parathyroid ade-
nomas and 1/1 for parathyroid hyperplasia.
For combined MIBI-PPS and PPTS, the sensitivity for
detection of parathyroid adenoma or parathyroid hyper-
plasia was 84% (32/38); 91% (31/34) for parathyroid ade-
noma and 25% (1/4) for parathyroid hyperplasia. The
PPV for detection of parathyroid adenoma or parathyroid
hyperplasia was 100% (32/32); 31/31 for parathyroid ade-
nomas and 1/1 for parathyroid hyperplasia.
The false-negative lesions were significantly smaller than
the true-positive ones by MIBI-PPS alone (0.77 ± 0.86 vs
1.84 ± 2.5 g, P = 0.03) and tended to be smaller also using
MIBI-PPS+PPTS (0.85 ± 1.13 vs 1.76 ± 2.44 g, P = 0.11).
The smallest parathyroid adenoma detected by both
imaging approaches weighed 0.2 g, while the smallest
hyperplastic gland detected weighed 0.5 g. All parathy-
roid adenomas missed by MIBI-PPS alone and by MIBI-
PPS+PPTS weighed ≤0.7 and ≤0.4 g, respectively. The
largest hyperplastic gland missed weighed 1.3 g.
There were no significant differences in sensitivity
between MIBI-PPS and MIBI-PPS+PPTS for the overall
patient population (P = 0.08) and for those with parathyroid
adenoma (P = 0.08). A reliable statistical comparison of the
sensitivity of both approaches for parathyroid hyperpla-
sia (both 25%) was not possible because of the very small
number of patients with parathyroid hyperplasia (n = 4).
There were also no significant differences in PPV between
MIBI-PPS and MIBI-PPS+PPTS for the overall patient
population (P > 0.99) and for those with parathyroid ade-
noma (P > 0.99). Here again, the very small number of
patients with parathyroid hyperplasia precluded any reli-
able statistical comparison of PPV in these patients. The
specificities and negative-predictive values were not deter-
mined because all patients had proven disease at surgery.
Figure 1 shows an example of a patient with a surgically
proven parathyroid adenoma that is positive both by
MIBI-PPS alone and by MIBI-PPS+ PPTS.
Figure 2 shows an example of a surgically proven para-
thyroid adenoma that is negative by MIBI-PPS alone, but
positive by MIBI-PPS+ PPTS indicating a rapid washout
parathyroid adenoma.
Figure 3 shows the surgically proven case of double ade-
noma demonstrated both by MIBI-PPS alone and by
MIBI-PPS+PPTS.
In the three patients with parathyroid hyperplasia with
false-negative MIBI-PPS and combined MIBI-PPS and
PPTS findings, the scans were completely negative
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
in one patient and showed only one focus of increased
uptake in each of the other two, thereby mischaracteriz-
ing them as having parathyroid adenoma rather than par-
athyroid hyperplasia.
Discussion
Parathyroid scintigraphy is one of the most widely used
imaging modalities for localization of suspected parathy-
roid adenoma and parathyroid hyperplasia [1–30,33–36].
While PET tracers, such as C-11 methionine and F-18
fluorocholine have more recently been utilized for this
purpose [33–36],Tc-99m MIBI scanning performed either
alone (dual-phase approach) or combined with Tc-99m
pertechnetate or I-123 thyroid scintigraphy (dual-tracer
approach) is by far the most widely employed scinti-
graphic approach [1–30].
Several imaging protocols have been employed using
Tc-99m MIBI with considerable variability in their diag-
nostic performance, particularly sensitivity [4–30]. The
Tc-99m MIBI component of these imaging protocols
can be broadly categorized into dual-phase parallel-hole
planar imaging, dual-phase pinhole planar imaging and
SPECT or SPECT/CT. Some protocols use I-123 or
Tc-99m pertechnetate thyroid scintigraphy either in
addition to dual-phase Tc-99m MIBI or combined only
with the early Tc-99m MIBI scan without performing a
delayed Tc-99m MIBI scan [4–6,8–10,13–18,20–27].
Despite the wide variability in the reported findings using
the different imaging protocols, several conclusions may
be drawn: first, dual-phase pinhole planar Tc-99m MIBI
scintigraphy is more sensitive than parallel-hole planar
Tc-99m MIBI scintigraphy [11–13]. Second, Tc-99m
MIBI SPECT and SPECT/CT appear to be more sen-
sitive than dual-phase parallel-hole planar Tc-99m
MIBI [5,7,14]. Third, the addition of I-123 or Tc-99m
pertechnetate thyroid scintigraphy to dual-phase planar,
SPECT or SPECT/CT Tc-99m MIBI generally results
in improved sensitivity compared with the corresponding
single-tracer, dual-phase approaches [6,8–10,13].
The current investigation in patients with biochemically
proven, mostly primary hyperparathyroidism compared
pinhole planar dual-phase Tc-99m MIBI (MIBI-PPS)
with a dual-tracer approach combining MIBI-PPS
with Tc-99m PPTS (MIBI-PPS+PPTS) to determine
whether the dual-tracer approach results in substantially
higher sensitivity and PPV, thereby justifying its routine
performance.
An important issue regarding our use of pinhole planar
imaging approach is whether its sensitivity and PPV is
inferior to SPECT or SPECT/CT and, if so whether it
is justified to use pinhole imaging in parathyroid scin-
tigraphy. Interestingly, there is no evidence that the pin-
hole planar approach is inferior to SPECT and there is at
least one study demonstrating that it is, in fact superior
 Tc-99m MIBI pinhole parathyroid scintigraphy Juweid et al.  5

Fig. 1

(a) Early mediastinal Tc-99m MIBI image. (b) Early Tc-99m MIBI pinhole neck image. (c) Delayed Tc-99m MIBI pinhole neck image. (d) Tc-99m
pertechnetate pinhole neck image. The early and delayed Tc-99m MIBI images show a small focus of increased uptake just lateral to the inferior
pole of the left thyroid lobe without a corresponding finding on the Tc-99m pertechnetate thyroid image consistent with a parathyroid adenoma.
Surgical exploration showed a 0.7-g parathyroid adenoma at the same location.

[16]. According to a recent meta-analysis of 24 studies
reported by Wong et al. [20], the pooled sensitivity of
dual-phase Tc-99m MIBISPECT for the identification of
parathyroid adenoma was 74% [95% confidence interval
(CI); 66–82%], which is not significantly different from
the pooled sensitivity of 70% (95% CI; 61–80%) using
the planar technique, including both parallel-hole and
pinhole collimation. The pooled sensitivity of pinhole
planar dual-phase Tc-99m MIBI for parathyroid ade-
noma is higher at 81% (214/265 parathyroid adenomas in
six studies comprising 258 patients) increasing slightly
to 84% (210/249 parathyroid adenomas in five studies
of 240 patients) with pinhole planar dual-tracer Tc-99m
MIBI [8,11–13,15,24,25]. These values are similar to
the respective values of 82 and 91% found in our study.
Although not always reported, the specificities (or PPVs)
appear to be similar between the Tc-99m MIBISPECT
and pinhole planar techniques, both generally exceed-
ing 90% [5,8,11,12,15,16]. Importantly, in an intrapatient
comparison, a sensitivity of 81% was found for detection
of parathyroid adenomas using pinhole planar Tc-99m
MIBI scintigraphy vs only 65% (P = 0.02) for Tc-99m
MIBI SPECT when both were combined with Tc-99m
pertechnetate thyroid scintigraphy [16]. The PPVs were
similar at 88 and 92%, respectively. Thus, there is ample
evidence that Tc-99m MIBI SPECT is not superior to
pinhole planar Tc-99m MIBI scintigraphy and that it
may, in fact, be inferior justifying the use of our approach
in the absence of a SPECT/CT device.
The situation is different in the case of SPECT/CT. The
aforementioned meta-analysis by Wong et al. [20] reported
a pooled sensitivity of 86% (95% CI; 81–90%) for dual-
phase Tc-99m MIBI SPECT/CT which was significantly
higher than those of SPECT and planar techniques. In

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6  Nuclear Medicine Communications  2019, Vol XXX No XXX

Fig. 2

(a) Early mediastinal Tc-99m MIBI image. (b) Early Tc-99m MIBI pinhole neck image. (c) Delayed Tc-99m MIBI pinhole neck image. (d) Tc-99m
pertechnetate pinhole neck image. The early Tc-99m MIBI image shows an area of mildly increased uptake adjacent to the inferior pole of the
left thyroid lobe that washes out on delayed Tc-99m MIBI image. The combination of early and delayed Tc-99m MIBI images alone (MIBI-PPS)
were, therefore, interpreted as negative for parathyroid adenoma. However, inspection of the Tc-99m pertechnetate thyroid image does not
show increased uptake corresponding to the early Tc-99m MIBI finding indicating that the area seen on early Tc-99m MIBI represents a rapid
washout parathyroid adenoma, resulting in a positive MIBI-PPS and PPTS scan combination. Surgical exploration showed a 3.7-g parathyroid
adenoma at the same location. MIBI-PPS, dual-phase Tc-99m MIBI pinhole parathyroid scintigraphy; PPTS, Tc-99m pertechnetate pinhole thyroid
scintigraphy.

intrapatient comparisons, Lavely et al. [5] found higher
sensitivity for dual-phase Tc-99m MIBI SPECT/CT
compared with dual-phase Tc-99m MIBI parallel-hole
planar (72 vs 56.5%, P < 0.0001) and SPECT (72 vs 61.5%,
P = 0.01) techniques in the detection of parathyroid ade-
noma. The PPV was also significantly higher for MIBI
SPECT/CT compared with dual-phase Tc-99m MIBI
parallel-hole planar imaging (87.3 vs 79%, P = 0.05) and
marginally higher compared with SPECT (87.3 vs 79.4%).
However, Neumann et al. [17] found significantly higher
specificity for SPECT/CT vs SPECT Tc-99m MIBI/I-123
thyroid scintigraphy (96 vs. 48%, respectively, P = 0.006)
[5]. A relatively recent intrapatient comparison between
pinhole planar and SPECT/CT Tc-99m MIBI/I-123
thyroid scintigraphy also showed significantly higher
specificity (100 vs 90%, P = 0.04) for SPECT/CT [18].
Although this study showed similar overall sensitivity for
both approaches (86% for SPECT/CT vs 75% for pinhole
planar imaging, P = 0.15), the sensitivity of SPECT/CT
was significantly higher (88 vs 62%, P = 0.04) in patients
with concomitant thyroid disease [18]. Thus, it appears
that when SPECT/CT is available, this imaging modality
performed with Tc-99m MIBI alone or combined with
I-123 or Tc-99m pertechnetate thyroid scintigraphy is
preferred over the pinhole planar approach because of
its greater specificity, presumably due to more accurate
anatomic localization of parathyroid lesions. In addition,
SPECT/CT appears to be particularly advantageous in
patients with concomitant thyroid disease [18]. However,
SPECT/CT is not universally available and, as discussed

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 Tc-99m MIBI pinhole parathyroid scintigraphy Juweid et al.  7

Fig. 3

(a) Early mediastinal Tc-99m MIBI image. (b) Early Tc-99m MIBI pinhole neck image. (c) Delayed Tc-99m MIBI pinhole neck image. (d) Tc-99m
pertechnetate pinhole neck image. The early and delayed Tc-99m MIBI images show a focus of increased uptake just below the inferior pole of the
left thyroid lobe. An additional focus of increased uptake adjacent to the inferior pole of the right thyroid lobe is only apparent on delayed Tc-99m
MIBI image. There are no corresponding findings on the Tc-99m pertechnetate thyroid image indicating that the two foci represent a double ade-
noma. Surgical exploration showed a 2.4-g left inferior pole parathyroid adenoma and a 0.3-g right inferior pole.

above, in this situation, the use of pinhole imaging is pre-
ferred over SPECT, an approach taken in our study. We
are aware that planar software zoom is sometimes used
to improve the resolution of planar parallel-hole images.
However, planar software zoom has not been reported
to substantially improve the lesion detectability in para-
thyroid imaging to an extent similar to pinhole imaging,
SPECT or SPECT/CT [12].
The current study has shown that the sensitivities and
PPVs of MIBI-PPS alone vs combined with PPTS are
statistically similar in all patients with a sensitivity and
PPV of 76 and 100%, respectively, using MIBI-PPS alone
vs 84 and 100% using MIBI-PPS+PPTS (Tables  2 and
3). The sensitivity for detection of parathyroid adenomas
was higher with both approaches (82% with MIBI-PPS
alone vs 91% with MIBI-PPS+PPTS), but here again no
significant difference in sensitivity was found. The PPV
for both approaches was also very high at 100% for both
imaging approaches. A reliable statistical comparison of
the sensitivity and PPV of both approaches for patients
with parathyroid hyperplasia was not possible due to
their very small number (n = 4), but the sensitivity of
25% computed for both approaches is in line with one
meta-analysis of planar and SPECT Tc-99m MIBI report-
ing a sensitivity of only 44% for parathyroid hyperplasia
vs 88% for parathyroid adenoma [23]. In fact, Thomas et
al. [7] reported an identical sensitivity (25%) to ours in
parathyroid hyperplasia using Tc-99m MIBISPECT vs
0% using parallel-hole planar dual-phase Tc-99m MIBI.
Our findings, at least in patients with parathyroid ade-
noma, do not justify the routine performance of thyroid
scintigraphy, but rather to perform it only if the dual-
phase study is equivocal. The most important example
of an equivocal finding is when the early Tc-99m MIBI

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8  Nuclear Medicine Communications  2019, Vol XXX No XXX
image shows a ‘hot’ or ‘warm’ focus (or foci) at the typ-
ical location of the parathyroid or intrathyroidal that
washes out partially or even completely on the delayed
image. In this case, it is critical to perform a thyroid scan
to determine whether there is a ‘mismatch’ between the
early Tc-99m MIBI image and the thyroid image with
respect to this focus (or foci), which would indicate a rap-
id-washout parathyroid adenoma (including an intrathy-
roidal one) or a ‘match’ consistent with thyroid nodule(s)
[7,28–30]. With this approach, our findings suggest that
Tc-99m MIBI pinhole parathyroid scintigraphy can yield
a sensitivity and a PPV exceeding 90% for parathyroid
adenoma detection, which is excellent for a planar imag-
ing technique and is superior to what has been reported
with SPECT imaging alone (without CT) [16,20].
As might be expected, the sensitivity of the pinhole pla-
nar dual-phase 99mTc-MIBI scintigraphic approach in
our study compares favorably with reported sensitivities
using parallel-hole planar dual-phase Tc-99m MIBI [11–
13]. For example, Thomas et al. [7] reported an overall
sensitivity of 42% (54% for parathyroid adenoma) using
the latter approach substantially lower than the 76% (82%
for parathyroid adenoma) found in our study. Lavely et
al. [5] also reported a 56.5% sensitivity for parathyroid
adenoma using the same approach. In an intrapatient
comparison, Tomas et al. [12] reported a 56% sensitiv-
ity with parallel-hole vs 89% with pinhole planar dual-
phase Tc-99m MIBI. Klingensmith III et al. [13] have
reported an even lower sensitivity of only 43.2% for par-
allel-hole planar dual-phase Tc-99m MIBI vs 66.2% for
pinhole collimation. While the sensitivity of dual-phase
parallel-hole imaging improves somewhat when I-123 or
Tc-99m pertechnetate thyroid scintigraphy is added, the
reported sensitivity remains below the sensitivity of the
corresponding approaches but with pinhole collimation
[10,13].
One limitation of our study is the relatively small num-
ber of patients included, but this is because we required
surgical exploration as this represents the ‘gold standard’
for assessment of the accuracy of the imaging approaches
tested. Had we enrolled a larger number of surgical
patients, the observed difference in sensitivity between
the dual-tracer and single-tracer approaches tested in
our study (8–9%) may have been statistically signifi-
cant. However, given the relatively small magnitude of
this difference, we do not believe that it would justify
performing a Tc-99m pertechnetate thyroid scan in all
patients. We also note that we did not have a sufficient
number of patients with parathyroid hyperplasia because
90% of patients in our study had primary hyperparathy-
roidism with reportedly only 10–15% incidence of par-
athyroid hyperplasia. Hence, the sensitivity and PPV of
the tested imaging approaches could not be reliably esti-
mated for parathyroid hyperplasia. Another limitation of
our study is that SPECT was not performed in addition
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
to pinhole imaging which would have allowed us to com-
pare the performance of both imaging approaches in the
same patients. However, our study was not designed
for this purpose and this may be addressed in a future
investigation.
Conclusion
Dual-phase pinhole planar Tc-99m MIBI parathyroid
scintigraphy has high sensitivity (82%) and PPV (100%)
for the detection of parathyroid adenomas, which are
similar to what has been reported in the literature using
this technique. The sensitivity and PPV for detection of
parathyroid hyperplasia cannot be reliably determined in
this study due to the very small number of patients with
this entity, but the low sensitivity observed is consistent
with the literature. When SPECT/CT is unavailable,
dual-phase pinhole planar Tc-99m MIBI is preferred over
SPECT due to its reported superior sensitivity with sim-
ilar PPV. The routine addition of thyroid scintigraphy to
dual-phase pinhole planar Tc-99m MIBI does not appear
to significantly improve its accuracy in the detection of
parathyroid adenomas or hyperplasia; it should therefore
be reserved for equivocal cases.
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