Comparison of Five Parathyroid Scintigraphic Protocols

Objectives. We compared five parathyroid scintigraphy protocols in patients with primary (pHPT) and secondary hyperparathyroidism (sHPT) and studied the interobserver agreement. The dual-tracer method (99mTc-sestamibi/123I) was used with three acquisition techniques (parallel-hole planar, pinhole planar, and SPECT/CT). The single-tracer method (99mTc-sestamibi) was used with two acquisition techniques (double-phase parallel-hole planar, and SPECT/CT). Thus five protocols were used, resulting in five sets of images. Materials and Methods. Image sets of 51 patients were retrospectively graded by four experienced nuclear medicine physicians. The final study group consisted of 24 patients (21 pHPT, 3 sHPT) who had been operated upon. Surgical and histopathologic findings were used as the standard of comparison. Results. Thirty abnormal parathyroid glands were found in 24 patients. The sensitivities of the dual-tracer method (76.7–80.0%) were similar (P = 1.0). The sensitivities of the single-tracer method (13.3–31.6%) were similar (P = 0.625). All differences in sensitivity between these two methods were statistically significant (P < 0.012). The interobserver agreement was good. Conclusion. This study indicates that any dual-tracer protocol with 99mTc-sestamibi and 123I is superior for enlarged parathyroid gland localization when compared with single-tracer protocols using 99mTc-sestamibi alone. The parathyroid scintigraphy was found to be independent of the reporter.


Introduction
99m Tc-methoxyisobutylisonitrile ( 99m Tc-sestamibi), �rst introduced by Coakley and coworkers as a parathyroid imaging agent in 1989 [1], is the imaging agent of choice for parathyroid scintigraphy (PS) [2]. Unfortunately, 99m Tcsestamibi is not a speci�c tracer for parathyroid tissue but is taken up by adjacent thyroid tissue. is problem can be overcome by using either a single-tracer (double phase) or a dual-tracer method.
In the single tracer method, it is assumed that thyroid and parathyroid tissues have different washout kinetics for 99m Tc-sestamibi [3]. By acquiring images in the early and late phases, the focally increasing uptake will reveal hyperfunctioning parathyroid tissue. In the dual-tracer method, 99m Tcsestamibi is used combined with 123 I or 99m Tc-pertechnetate, which are taken up by the thyroid gland only. Subtracting the thyroid image from the 99m Tc-sestamibi image provides visualization of the parathyroid tissue alone [4].
With both single-tracer and dual-tracer methods, several acquisition techniques can be used (i.e., planar acquisitions with parallel-hole or pinhole collimators and SPECT or SPECT/CT), and several choices can be made about the settings used for each technique (e.g., matrix size, energy 2 International Journal of Molecular Imaging settings, and acquisition time). ere are several studies that provide comparisons between the different imaging methods or techniques, although there is little evidence supporting the superiority of one over another, resulting in the use of various study protocols today [5,6].
�e have previously shown that there is signi�cant variability in the current practice of PS in Finland [7]. is is also true in other countries, with reported sensitivities for localizing abnormal parathyroid tissue ranging from 34% to 100% [8].
As a result of our previous study, the clinical protocol of parathyroid scintigraphy in Satakunta central hospital was changed in June 2010. Pinhole and SPECT/CT acquisition techniques were included to increase the sensitivity of the study. Additional late phase imaging was also included to bene�t from the double phase method as well.
e goal of this study was to compare the sensitivity and speci�city of a single-tracer method and a dualtracer method with various acquisition techniques. e dual-tracer method ( 99m Tc-sestamibi/ 123 I) was used with three acquisition techniques (parallel-hole planar, pinhole planar, and SPECT/CT). e single-tracer method ( 99m Tcsestamibi) was used with two acquisition techniques (double phase parallel-hole planar, and SPECT/CT). In addition, the agreement between the �ndings of four experienced nuclear medicine physicians was studied.

2.1.
Patients. is was a retrospective single-center study of �y-one patients referred for PS between June 2010 and February 2011 in Satakunta Central Hospital, Finland. Patient data were included if there was biochemical evidence of hyperparathyroidism, if scintigraphy was requested for preoperative tumor localization, and if the patient proceeded to surgery. Histopathological �nding was used as the gold standard. e �nal study group consisted of 6 men and 18 women with a mean age of 62.3 years (range, 32.1-86.8 years). Twenty-one patients had pHPT. Preoperative plasma intact parathyroid hormone (iPTH) values ranged from 69 ng/L to 277 ng/L (mean 190 ng/L, normal values 10-65 ng/L), and values for preoperative serum calcium (Ca) ranged from 1.37 mmol/L to 1.73 mmol/L (mean 1.48 mmol/L, normal values 1.16-1.3 mmol/L). ree patients had sHPT due to renal failure. Preoperative iPTH values ranged from 210 ng/L to 400 ng/L (mean 380 ng/L), values for preoperative Ca ranged from 1.21 mmol/L to 1.8 mmol/L (mean 1.45 mmol/L). Twenty-seven patients did not proceed to surgery for a variety of reasons (patient condition, death, and other illnesses). is study was exempt from institutional review board approval according to Finnish legislation. Informed consent was waived.

Imaging: Doses and Acquisition.
Patients received 20 MBq of 123 I (MAP Medical Technologies) intravenously. Two hours later, 550 MBq of 99m Tc-sestamibi (Mallinckrodt Medical B.V.) was injected intravenously. Ten minutes aer the 99m Tc-sestamibi administration, imaging was started.
Five different image sets were acquired. e order and the timing (aer the injection or 99m Tc-sestamibi) of the acquisitions and the resulting image sets are presented in Figure 1.
First, a static 10-minute anterior image of the neck and chest was acquired using a low-energy, high-resolution, parallel-hole collimator (LEHR) (256 × 256 matrix; 1.85x zoom). Next, a static 10-minute anterior image of the neck was acquired from a distance of 10 cm from the patient's skin using a 5 mm diameter pinhole collimator (256 × 256 matrix; 2.19x zoom). Acquisitions were performed with the same dual-head gamma camera (Skylight; Philips). All data were collected in dual-energy windows. e 99m Tc window was centered at 140 keV and had a 10% width (range, 133-147 keV). e 123 I window was centered at 159 keV and had a 10% width (range, 151-167 keV). Narrow windows were used to minimize crosstalk between isotopes.
One hour aer the 99m Tc-sestamibi injection, the SPECT/CT acquisition was started (Symbia T; Siemens). SPECT data were acquired in a step-and-shoot sequence with a noncircular orbit (180 ∘ detector con�guration; lowenergy, parallel-hole, high-resolution collimators; 128 × 128 matrix; 4.8 mm pixel size; 48 views for each detector (3,75 ∘ per projection); 33 s/projection; total scan time, 32 min). All data were collected in dual-energy windows. e 99m Tc window was centered at 140 keV and had a 15% width (range, 129.5-150.5 keV). e 123 I window was placed with a 4% offset above 159 keV and had a 15% width (range, 153.4-177.3 keV). e 4% offset was used to minimize the spillover of the 99m Tc photopeak into the 123 I photopeak. Aer the SPECT acquisition was complete, the patient remained still on the table for the CT acquisition. A topogram scout scan (130 kVp, 30 mA, anterior view) was performed �rst, and limits for the CT acquisition were set (from the neck to the diaphragm). en, a helical CT scan was performed (130 kVp, 2 × 2.5 mm collimation, 0.8 s rotation time, 1.5 pitch). e dose was controlled by tubecurrent modulation (CARE Dose AEC+DOM; Siemens), with the reference exposure set to 30 mAs.
Finally, a static 10-minute anterior image of the neck and chest was acquired using a low-energy, high-resolution collimator with a Siemens Symbia T-gamma camera (256 × 256 matrix; 1.85x zoom (32.2 cm �eld)). e same energy settings as those in the SPECT acquisition were used. Eleven of the patients did not complete this �nal image due to limited camera time or patient-related reasons. A 99m Tc intrinsic �ood was used for both energy windows in both cameras. It was veri�ed that the image-�eld uniformity was acceptable for all energy windows used.

Image Processing.
All planar images were analyzed in a Hermes workstation (Hermes Medical Solutions). For dualtracer images, a normalization factor (NF) was de�ned as the ratio of the thyroid maximum pixel counts in the 123 I and 99m Tc-sestamibi images. Gradient subtraction images were created by multiplying the 99m Tc-sestamibi image with 10  the original NF), and the 123 I image was subtracted from each normalized 99m Tc-sestamibi image, resulting in 10 subtraction images to avoid oversubtraction [9,10]. e �nal image sets consisted of 99m Tc-sestamibi and 123 I images and gradient subtraction images (image set 1 acquired with LEHR, image set 2 with pinhole). 99m Tc-sestamibi early-and late-phase images were displayed side-by-side on the Hermes workstation (image set 3). SPECT images were reconstructed on the Siemens Syngo workstation (Siemens) using the FLASH 3D algorithm (8 iterations, 8 subsets, �aussian 9.00 �lter). No scatter correction was used. e initial NF was de�ned as the ratio of the corresponding thyroid maximum voxel counts in 99m Tcsestamibi and 123 I SPECT data. 123 I SPECT data were multiplied by NF to create normalized 123 I SPECT data, which were then subtracted from 99m Tc-sestamibi SPECT data to create the subtraction SPECT dataset, as described by Neumann and coworkers [4]. e NF was adjusted until the subtraction SPECT images were subjectively satisfactory. CT data were reconstructed on the Siemens Syngo workstation (Siemens) for attenuation correction using the B08s kernel, and for fusion display purposes with a B40s medium kernel. e CT images were downsampled to match the SPECT image matrix and converted from Houns�eld units into e�ective attenuation values at 140 keV ( 99m Tc) and 159 keV ( 123 I). e �nal image sets consisted of 99m Tc-sestamibi SPECT/CT data (image set 4) and 123 I, 99m Tc-sestamibi, and subtraction SPECT/CT data (image set 5). e accuracy of the SPECT/CT data coregistration was checked. All image processing was performed by an experienced medical physicist.

Image Interpretation.
All patient image datasets were anonymized before review by four experienced nuclear medicine physicians, who were blinded to all patient-related information. Five image sets ( Figure 1) were reviewed. Datasets 1, 2, and 3 were read in separate reading sessions. Image sets 4 and 5 were reviewed in a single session in this order, with the physician being aware that the datasets belonged to the same patient.
Each quadrant in relation to the thyroid gland (right upper, right lower, le� upper, and le� lower) was classi�ed on a 3-point scale (0 = negative, 1 = uncertain, and 2 = positive). e image review criteria for positive �nding were as follows: (a) for image sets 1 and 2: clear abnormal residual activity on the planar subtraction images, (b) for image set 3: focally increased uptake that persisted or increased in intensity from early to late images, (c) for image set 4: focally increased uptake outside the normal 99m Tc-sestamibi biodistribution that had an anatomic correlation in the CT images, and (d) for image set 5: clear abnormal residual activity on the subtraction SPECT images that had an anatomic correlation in the CT images.

Surgery and Histologic Analysis.
All patients were operated upon by an endocrine surgeon using an open technique. e surgeon was aware of all initial scintigraphic results prior to surgery. All glands were not identi�ed for all patients. Postoperative iPTH and Ca values were reviewed to con�rm surgery success. e mean interval between scintigraphy and surgery was 181 days (range, 29-457 days). A histopathological analysis was performed for all excised tissue.

Data Analysis.
To estimate the sensitivity, speci�city, and accuracy for the localization for each image set, scores of 0-1 were considered negative and scores of 2 were considered positive. Findings were classi�ed as true positive, false positive, true negative, or false negative with histologic analysis as the reference standard. For each patient, four scores, one for each quadrant, were assigned. e false-positive image rate was de�ned as the ratio of false positives to the sum of true positives plus false positives [11].

Statistical
Methods. e sensitivity, speci�city, and accuracy of each image set were calculated for each physician separately. A McNemar test was performed to compare the sensitivities, speci�cities, and accuracies between the image sets. e results from physician 1 were chosen when comparing the image sets, as he had the most experience with the imaging methods and techniques used. e Mann-Whitney nonparametric test was used to compare the size of the visualized and nonvisualized glands. A McNemar test was also used to analyze the accuracy of the different physicians. e differences for each method/technique were analyzed separately. coefficients were used to quantify the agreement between the results from the four physicians. Positive kappa values within the ranges of 0.01-0.20, 0.21-0.4, 0.41-0.60, 0.61-0.80, and 0.81-1.00 were interpreted as "very weak, " "weak, " "medium, " "good, " and "very good" agreement, respectively [12]. A value <0.05 was considered statistically signi�cant. Statistical analyses were conducted using SAS 9.2 (SAS Institute Inc., Cary, NC, USA) and SPSS statistical analysis soware (SPSS Inc., Chicago, IL, USA).

Histological Findings.
Altogether, 30 enlarged glands were found in 24 patients. Twenty patients had a solitary parathyroid adenoma, two patients had double adenomas, and two patients had multiglandular disease. e mean weight of the abnormal parathyroid glands was 677 mg (weight information was not available for four glands).
e postoperative serum Ca values were normalized for all patients. e postoperative iPTH values were normalized for 17 patients. For 7 patients, these values were slightly elevated (ranged from 80 ng/L to 134 ng/L (mean 90 ng/L), but decreased from the preoperative values (ranged from 138 ng/L to 400 ng/L (mean 165 ng/L)). Four glands were visualized in the operation for these patients.
e pathological �ndings together with the image �ndings for physician 1 are listed in Table 1. 123 I/ 99 c-Sestamibi. All image sets with 123 I/ 99m Tc-sestamibi were signi�cantly more sensitive than any image set with 99m Tc-sestamibi, regardless of the acquisition technique (Tables 2 and 3). 99m Tc-sestamibi SPECT/CT (image set 4) had the highest speci�city (100%), as there were no false-positive readings ( Table 2).

Planar AP with LEHR versus Planar AP with
Pinhole versus SPECT/CT. ere was no difference in the sensitivity, speci�city, or accuracy between the acquisition techniques using 99m Tc-sestamibi alone. ere was also no difference in the sensitivity, speci�city, or accuracy between the acquisition techniques using 123 I/ 99m Tc-sestamibi (Tables 2 and 3).
Although there was no difference in the sensitivity, SPECT/CT may offer invaluable three-dimensional information about the location of the enlarged parathyroid adenomas together with anatomical information (Figure 3).  Table 4.
Four of these were due to cold thyroid nodules in 123 I images, causing erroneous interpretation in the subtraction image ( Figure 4). Uneven 123 I uptake caused thus 55% of all false-positive �ndings.
One patient had clear uptake in the 99m Tc-sestamibi image below the thyroid as seen in planar images. All physicians interpreted this as a positive �nding in the planar images. In the SPECT/CT images, it was revealed that the uptake was in the cervical vertebra ( Figure 5). is bone uptake caused 20% of all false-positive �ndings.
ree false positive �ndings were due to the "edge effect" in 123 I/ 99m Tc-sestamibi subtraction SPECT/CT images (residual activity around the thyroid lobes aer subtraction). is artefact caused 10% of all false-positive �ndings.
Four positive �ndings were caused by an error in image interpretation, mainly in double phase 99m Tc-sestamibi images. Difficulty in setting the line between the positive and the negative �ndings caused 15% of all false-positive �ndings.
As seen in Table 4, 123 I/ 99m Tc-sestamibi dual-tracer method with various acquisition techniques produced 90% of all false-positive �ndings. Subtraction SPECT/CT yielded the lowest percentage of false positives when compared to the other subtraction methods. e double phase 99m Tcsestamibi method produced only 10% of all false-positive �ndings. e false-positive image rate (%) is presented in Table 5.

False-Negative Findings.
ere was only one abnormal parathyroid gland (number 10, Table 1) that was visualized in all image sets and by all of the physicians. us 23 patients had 29 different false-negative �ndings (267 false-negative �ndings if all physicians and image sets are summed up). 99m Tc-sestamibi/ 123 I subtraction planar images with parallel-hole collimator produced 13.9% of all falsenegative �ndings, 99m Tc-sestamibi/ 123 I subtraction planar images with pinhole collimator produced 9.7% of all falsenegative �ndings, 99m Tc-sestamibi double phase images with parallel-hole collimator produced 22.8% of all false-negative International Journal of Molecular Imaging 5 T 1: Number of adenomas and hyperplastic glands and image �ndings for physician 1.

Patient number
Gland number Weight (mg)  Findings for image set  1  2  3  4  5  1  1  170  FN  FN  NA  FN  FN  1  2  570  TP  TP  NA  FN  TP  2  3  980  TP  TP  FN  FN  TP  3  4  830  TP  TP  FN  TP  TP  4  5  1280  TP  TP  FN  FN  TP  4  6  840  TP  FN  FN  FN  TP  4  7  2140  TP  TP  FN  FN  TP  5  8  NA  TP  TP  NA  FN  TP  6  9  1200  TP  TP  NA  FN  TP  7  10  960  TP  TP  TP  TP  TP  8  11  1880  TP  TP  TP  FN  TP  9  12  1160  FN  TP  FN  FN  FN  10  13  299  TP  TP  FN  FN  TP  11  14  200  FN  FN  FN  FN  FN  12  15  260  TP  TP  FN  FN  TP  13  16  570  TP  TP  TP  TP  TP  14  17  370  TP  TP  FN  FN  TP  15  18  300  TP  FN  NA  FN  FN  15  19  400  TP  TP  NA  FN  TP  15  20  NA  TP  TP  NA  FN  TP  16  21  510  TP  TP  NA  FN  TP  17  22  340  TP  TP  FN  FN  TP  18  23  NA  TP  TP  TP  FN  TP  19  24  420  FN  FN  TP  FN  FN  20  25  300  FN  TP  NA  FN  FN  20  26  NA  TP  TP  NA  FN  TP  21  27  520  TP  TP  NA  FN  TP  22  28  400  TP  TP  FN  FN  TP  23  29  550  TP  TP  TP  TP  TP  24  30  160  FN  FN  FN   �ndings, 99m Tc-sestamibi SPECT/CT produced 39.3% of all false-negative �ndings, and 99m Tc-sestamibi/ 123 I subtraction SPECT/CT produced 14.2% of all false-negative �ndings (all physicians and all image sets are summed up). e smallest gland located in this series was 260 mg. ere were three smaller abnormal parathyroid glands (160 mg, 170 mg, and 200 mg) that could not be located with any method or imaging technique by any of the physicians. e mean gland size of false-negative and true-positive �ndings for all physicians and image sets are presented in Table 6 together with the statistical signi�cance.
3.6. Interobserver Variability. e coefficient for the agreement of the results between the four physicians for the �ve study readings are shown in Table 7. e highest agreement for accuracy was found for 99m Tcsestamibi SPECT/CT, which did not have any false-positive �ndings for any physician. e highest agreement for sensitivity was found for the planar subtraction images of 123 I/ 99m Tc-sestamibi with the pinhole collimator.

Discussion
Our results clearly show that a dual-tracer method with 99m Tc-sestamibi and 123 I is superior to a single-tracer method with 99m Tc-sestamibi for PS, regardless of the acquisition technique used. is has been proposed by other authors as well [4,9,13,14].
To our �nowledge, this is the �rst study comparing planar imaging with parallel-hole and pinhole collimators using the    Tc-sestamibi subtraction method with patients. We could not demonstrate the improved sensitivity from the use of the pinhole collimator that has been shown by several authors when using 99m Tc-sestamibi [15][16][17][18][19][20]. SPECT alone has been shown to improve sensitivity compared with planar imaging with parallel-hole collimators [6,[21][22][23][24]. SPECT/CT has been shown to offer precise anatomical localization and an improvement in diagnostic speci�city and accuracy over conventional SPECT, especially for patients with previous neck surgery or multiglandular disease [5,[25][26][27][28][29][30][31][32]. e use of SPECT/CT also shortens surgical times (when compared with SPECT alone) and eventually lowers costs [33,34]. Opposite opinions have also been presented, and the use of SPECT/CT has been found to be important only for locating ectopic parathyroid adenomas [35,36].
We could not demonstrate an increased sensitivity for 123 I/ 99m Tc-sestamibi subtraction SPECT/CT when compared with planar 99m Tc-sestamibi/ 123 I subtraction image sets. However, the use of 123 I/ 99m Tc-sestamibi SPECT/CT decreased the false-positive rate for three observers when compared with planar 123 I/ 99m Tc-sestamibi image sets.
e low sensitivity of double phase planar 99m Tcsestamibi or 99m Tc-sestamibi SPECT/CT cannot be explained by the rapid washout of 99m Tc-sestamibi, as 19 enlarged parathyroid glands were visible in 123 I/ 99m Tc-sestamibi SPECT/CT images that could not be visualized with 99m Tcsestamibi SPECT/CT. A low sensitivity for a single tracer or the double phase protocols has also been reported by other authors [3,37].
e low sensitivity of the 99m Tc-sestamibi SPECT/CT in this study could not be linked to the timing of the acquisition. SPECT acquisition was started approximately one hour aer 99m Tc-sestamibi injection. Lavely and coworkers were able to demonstrate much better sensitivity for early-phase SPECT/CT (62%) and also for early planar/delayed planar imaging (56,5%) [5]. e timing of their early planar and SPECT/CT acquisitions was almost identical to ours.
Our results for the 123 I/ 99m Tc-sestamibi subtraction SPECT/CT are comparable to the results of Neumann and coworkers [26], who demonstrated a sensitivity of 70% and a speci�city of 96% in a group of 61 patients with primary hyperparathyroidism. e increase of speci�city (when compared with SPECT alone) was explained by reducing the number of false positives.
ere were three abnormal parathyroid glands that were visible in 123 I/ 99m Tc-sestamibi subtraction planar images (with a parallel-hole or a pinhole collimator) but not visible in 123 I/ 99m Tc-sestamibi subtraction SPECT/CT. is could be due to rapid washout [38] as SPECT/CT was performed one hour later than the planar images were acquired. us, the timing of the various acquisitions should be considered carefully, and SPECT/CT should be performed in the early phase so as not to miss abnormal parathyroid gland(s) with rapid washout [10].
e average false-positive rate was comparable to previous reports [6,11]. In this retrospective study, the �ve image sets were not reviewed together, which is normally done in our clinical scenario. With careful observation of the 123 I images of the thyroid, it should be possible to decrease the false-positive rate in subtraction images.
It seems that a major factor in�uencing detection of abnormal parathyroid glands is their size. e difference of mean gland size of false-negative and true-positive �ndings was statistically signi�cant for all protocols used in this study.
ere was lower number of ectopic glands in this patient group than could be expected [39]. ere might have been small ectopic glands which were not recognized in scintigraphy or in surgery. is might explain the slightly elevated iPTH values for 7 patients.
Several imaging protocols for PS with 99m Tc-sestamibi are in use, with a wide range of sensitivities (34-100%) reported [8]. No large study exists that compares the accuracy of each [6]. We have shown the superiority of the 123 I/ 99m Tc-sestamibi subtraction method of PS. e high popularity of the single-tracer method with 99m Tc-sestamibi alone can only be explained by its technical simplicity. It is true that the 123 I/ 99m Tc-sestamibi subtraction method, especially SPECT/CT, is technically demanding. ere are several possible sources of artifacts, such as scaling and the subtraction process. In our opinion, the data processing should be performed by an experienced medical physicist.
Even optimal processing of identical 99m Tc and 123 I targets does not give �awless subtraction image, some activity is always le around the edges. In this series, it was in few cases interpreted as a positive �nding. To our knowledge, this artefact has not been described earlier concerning parathyroid scintigraphy [40].
e overall interobserver agreement in this study was good. e average coefficient was 0.79 for accuracy and 0.70 for sensitivity. ese results are comparable to previous results [12,15].
One of the main limitations of this study is the number of patients in the image set 3 ( 99m Tc-sestamibi double phase images). Another limitation of our study relates to the fact that the delay phase was acquired with another gamma camera. However, quality assurance measurements are routinely performed for both cameras. ere are no differences in important parameters regarding image quality.
e clinical PS protocol presented in this study, which included various acquisitions, is quite time consuming. e discomfort for the patient should be decreased by rejecting unnecessary acquisitions. is study indicates that the 123 I/ 99m Tc-sestamibi subtraction method combined with any imaging technique is adequate to locate abnormal parathyroid glands. However, 123 I/ 99m Tc-sestamibi subtraction SPECT/CT is recommended because it provides accurate three-dimensional information about the location of enlarged parathyroid adenomas together with anatomical information ( Figure 3) and may in�uence the surgical approach [14]. With SPECT/CT, it is also possible to avoid some false-positive �ndings resulting from the 99m Tcsestamibi uptake in bone structures. e additional use of anterior pinhole images may be useful for recognizing cold thyroid nodules and thus further reducing the false-positive rate. Determining the optimal technical aspects (acquisition and processing parameters, various physical corrections) still requires further study.

Conclusion
e results of this study show that the 123 I/ 99m Tc-sestamibi subtraction method combined with any imaging technique is superior for enlarged parathyroid gland localization when compared with 99m Tc-sestamibi alone with any acquisition technique. 123 I/ 99m Tc-sestamibi subtraction SPECT/CT is recommended because it provides accurate three-dimensional information about the location of enlarged parathyroid adenomas. e use of anterior pinhole images may be useful for recognizing cold thyroid nodules and thus reducing the false-positive rate. e overall interobserver agreement for accuracy and for sensitivity in this study was good. us the parathyroid scintigraphy is independent of the reporter.
ere are two limitations that need to be acknowledged regarding this study. e �rst limitation is the number of patients in the 99m Tc-sestamibi double phase group. Another limitation relates to the fact that the delay phase was acquired with another gamma camera.