Quantitative comparison of technetium-99m tetrofosmin and thallium-201 images of the thyroid and abnormal parathyroid glands

The aim of the study was to quantitatively compare the scintigraphic images of the thyroid and abnormal parathyroid glands obtained with technetium-99m tetrofosmin and thallium-201 in patients with hyperparathyroidism. Forty-six patients with hyperparathyroidism underwent ²⁰¹Tl (74 MBq), ^99mTc-pertechnetate (74 MBq) and ^99mTc-tetrofosmin (555–740 MBq) scintigraphy in a single session. Image analysis included the computation of the thyroid/background ratio in the whole study population and the parathyroid/background ratio, parathyroid/thyroid ratio and diagnostic sensitivity in 17 patients who underwent parathyroid surgery. The pertechnetate subtraction technique was used. ²⁰¹Tl and ^99mTc-tetrofosmin showed a similar thyroid/background ratio (1.79±0.41 and 1.81±0.47, respectively, P=NS); however, ^99mTc-tetrofosmin showed a higher parathyroid/background ratio than ²⁰¹Tl (2.06±0.54 vs 1.79± 0.50, P=0.007). Despite the superior quality of ^99mTc-tetrofosmin images, both tracers showed identical sensitivity in detecting enlarged parathyroid glands in patients with primary hyperparathyroidism (89%) and in those with secondary hyperparathyroidism (50%).     

Parathyroid scintigraphy: comparison of technetium-99m methoxyisobutylisonitrile and technetium-99m tetrofosmin studies

We report the preliminary results of a prospective study demonstrating tetrofosmin uptake in surgically and histologically proven parathyroid adenomas. In ten patients with primary chronic hyperparathyroidism, parathyroid imaging was performed using (1) technetium-99m methoxyisobutylisonitrile (MIBI) and (2)^99mTc-1,2-bis(bis(2-ethoxyethyl)phosphino)ethane (tetrofosmin) within a time interval of 3–5 days. Both tracers correctly identified the parathyroid adenomas by focal prolonged tracer retention. On visual inspection image contrast was generally higher with MIBI than with tetrofosmin in all the patients studied. Tetrofosmin showed a slower elimination from the parathyroid adenomas than MIBI in six of the ten cases. Our preliminary results show that tetrofosmin, like MIBI, as a feasible, sensitive tracer for parathyroid scintigraphy. For routine use, the rapid kit preparation without heating and the lower radiation dose to the patient make tetrofosmin an alternative tracer for parathyroid scintigraphy. Further evaluation is needed to determine which of the two tracers is the more sensitive for the detection of parathyroid adenomas, and which tracer properties better reflect the degree of endocrine activity.[/p]     

Misinterpretation of the upper parathyroid adenoma on thallium-201/technetium-99m subtraction scintigraphy.

Pre-operative thallium-technetium subtraction scintigraphy of 50 patients with primary hyperparathyroidism, which was subsequently proven on histology to be due to an adenoma, was compared with operative findings. Six scans were negative and seven uninterpretable. Of the remaining 37 patients, 34 had correct scan prediction of the anatomical locations of the adenomas. On examination of the origins of the adenomas, all six scintigraphic predictions of upper adenomas corresponded to tumours arising from the upper gland found at operation. Of the 25 lower predictions, there was one false positive and 16 were correct, i.e. of lower gland origin, but eight were found to originate from the upper gland. This misinterpretation is though to be due to the prolapse of an adenoma arising from the upper gland towards the lower pole of the thyroid, thereby mimicking a lower lesion on the scan.     

Fetal adenoma of the thyroid. A common source for false-positive thallium-201/technetium-99m pertechnetate subtraction parathyroid scintigraphy

The specificity of thallium/technetium imaging for the localization of parathyroid tumors has remained high. False-positive findings usually arise from an incorrectly perceived mismatch. In these case reports, false-positive findings resulted from the presence of intrathyroidal fetal adenomas. Benign thyroid adenomas appear to represent a common source of false-positive finding for parathyroid tumor in thallium/technetium imaging.     

A parathyroid cyst with adenoma on thallium-201/technetium-99m subtraction imaging

A case of a parathyroid cyst with adenoma was seen on Tl-201/Tc-99m subtraction imaging. The literature regarding parathyroid cysts and the subtraction technique for parathyroid adenoma imaging was reviewed.     

Technetium-99m tetrofosmin imaging in thyroid diseases: comparison with Tc-99m-pertechnetate,thallium-201 and Tc-99m-methoxyisobutylisonitrile scans

Technetium-99m tetrofosmin is a lipophilic phosphine used for myocardial perfusion imaging. Biodistribution studies have shown significant thyroid uptake of tetrofosmin and preliminary reports have suggested that tetrofosmin imaging may be of value in patients with thyroid cancer. In this study, tetrofosmin whole-body scintigraphy was performed in 35 patients with evidence of thyroid diseases. All patients underwent laboratory evaluation of thyroid function as well as^99mTc pertechnetate scan, thallium-201 (n=16)^99mTc-methoxyisobutylisonitrile (MIBI) (n=19) whole-body studies. Thyroid images were semi-quantitatively analysed by a 4-point score: O=no significant uptake; 1=uptake increased as compared to background activity, but inferior to normal thyroid tissue; 2=uptake equal to normal thyroid tissue; 3=uptake superior to normal thyroid tissue. Pathology examinations were obtained. A total of 41 thyroid nodules were detected, of which 15 were goitre nodules, 13 adenomas and 13 malignant lesions. In goitre nodules, concordant results of tetrofosmin and pertechnetate uptake (score 1 or 0) were observed in the majority of lesions (87%). In function adenomas (n=10), both tetrofosmin uptake and pertechnetate uptake were score 3. In non-function adenomas (n=3), tetrofosmin uptake was score 3, while pertechnetate uptake was score 0. In six malignant lesions, tetrofosmin uptake was score 3, while pertechnetate uptake was score 0; in the other seven lesions, where a prevalence of goitre abnormalities was observed, results of tetrofosmin and pertechnetate uptake were similar (score 0 or 1). In seven (70%) of the ten patients with malignant nodules, whole-body tetrofosmin images showed increased abnormal uptake in a total of 28 extra-thyroid tumour sites, as subsequently confirmed by other techniques. When tetrofosmin images were compared to 201T1 and^99mTc-MIBI scans, concordant results were observed in all cases. In conclusion, tetrofosmin imaging may be particularly useful to characterize and stage patients with malignant thyroid nodules; it shows similar results to thallium but provides better image quality. Comparable findings were observed between tetrofosmin and MIBI studies. Thus, tetrofosmin may be an alternative to thallium and MIBI in the aforementioned patients.     

Quantitative planar imaging with technetium-99m methoxyisobutyl isonitrile: comparison of uptake patterns with thallium-201

To compare the myocardial uptake pattern of 99mTc-labeled methoxyisobutyl isonitrile [( 99mTc] MIBI) and 201TI, planar scintigraphy were performed in both patients with documented coronary artery disease and subjects with a low likelihood of disease. Quantitative analysis was employed using a standard interpolative background subtraction algorithm and a new algorithm modified to better accommodate for the differences in extracardiac activity seen with [99mTc]MIBI rest images. Among patients with coronary artery disease, the standard algorithm yielded no significant difference in relative defect magnitude between [99mTc]MIBI and 201TI on stress scintigrams (p = 0.48), although the magnitude of [99mTc]MIBI defects was greater on resting images (p = 0.02). When the modified algorithm was employed, defect magnitude was similar for both stress (p = 0.91) and rest (p = 0.20) images. Normal segmental uptake ratios derived from a comparison of contralateral segments (e.g., septal:posterolateral) in the low likelihood patients were similar for both [99mTc]MIBI and 201TI. Thus, modification of the standard interpolative background subtraction algorithm is necessary for quantitative planar [99mTc]MIBI perfusion imaging. When appropriate background subtraction is employed, myocardial uptake and quantitative defect magnitude of [99mTc]MIBI and 201TI planar images are similar.     

Localization of enlarged parathyroid glands by thallium-201 and technetium-99m subtraction imaging. Gland mass and parathormone levels in primary hyperparathyroidism

Twenty-two patients, all with surgically proven primary hyperparathyroidism, were studied by TI-201 thallous chloride and Tc-99m pertechnetate subtraction imaging. Fifteen parathyroid adenomata and one hyperplastic gland between 0.33 and 14.8 g were correctly localized in 16 patients. Two adenomata and seven hyperplastic or histologically normal parathyroids between 0.1 g and 1.4 g in seven patients were not localized. One patient had a correctly localized 13.0-g adenoma with a nonlocalized 0.3 g hyperplastic parathyroid gland and there were two false positive localizations. Sensitivity was 64% (glands), and 73% (patients). There was only fair correlation with parathormone (PTH) levels, but these were elevated in all but four of the patients with correctly localized parathyroids. The authors conclude that the imaging procedure is useful but its sensitivity is limited by difficulty in localizing correctly small glands, particularly those of less than 0.5 g, which comprised 29% of those excised.     

Evaluation of thyroid nodules with technetium-99m tetrofosmin dual-phase scintigraphy

Technetium-99m tetrofosmin, a lipophilic cationic complex molecule, was introduced for myocardial imaging. In some biodistribution studies it has also been reported to accumulate in the thyroid gland. Our objectives were to determine which thyroid nodules retain tetrofosmin and whether preoperative evaluation of malignancy is possible. Tetrofosmin scintigraphy was performed in 57 patients with a cold thyroid nodule on previously performed pertechnetate scintigraphy. All patients had undergone ultrasonography and sonographically guided fine-needle aspiration biopsy. The tetrofosmin scintigrams were obtained 5 min (early image) and 1 h (late image) after intravenous injection of 370 MBq. Only nodules that showed clear tracer retention after 1 h in comparison with retention at 5 min were classified as TETRO positive. Nodules without late retention were classified as TETRO negative. All patients underwent surgery and the histological results were compared with the results of tetrofosmin scintigraphy. Ten out of 11 patients with thyroid carcinoma (two pT1, three pT2, five pT4) were TETRO negative. One patient with papillary carcinoma (pT2) was TETRO positive. The mean nodular to thyroid tissue (N/T) ratio for the late scan was 1.0±0.20. There were 21 patients with thyroid adenomas (seven follicular, seven microfollicular and seven oxyphilic); 15 of these patients were TETRO positive and six TETRO negative. The mean N/T ratio for the late images was 1.34±0.41. All patients with degenerative goitre (24 cases) and the one patient with Hashimoto's disease were TETRO negative after 1 h and the N/T ratio was 0.92±0.12 on the late scan. Our results indicate that^99mTc-tetrofosmin scanning is of little value preoperatively in distinguishing thyroid carcinoma from other thyroid nodules. Tetrofosmin tends to demonstrate thyroid adenomas but does not have a routine role in the assessment of thyroid nodules.     

Adsorption of technetium-99m tetrofosmin and technetium-99m furifosmin on plastic syringes

Some groups have reported that adsorption of radiopharmaceuticals on disposable plastic syringes can reach levels of almost 50%. This high loss of radioactivity stimulated us to carry out similar studies. Our measurements were done in combination with patient studies. Therefore, we used 2-ml syringes, all of the same brand. The radioactivity in the syringe was measured immediately before and after injection. a total of 500–600 MBq technetium-99m labelled tetrofosmin or technetium-99m furifosmin was administered to 48 patients using four different injection techniques (n = 6 for each technique with each tracer): with needles, 1 min blood incubation at 22°C, 10 or 30 min after preparation of the tracer; with butterflies, 1 min blood incubation at 22°C, 10 or 30 min after preparation of the tracer. Neither in syringes nor in needles or butterflies did more than 7% of the initial radioactivity remain. The entire residual activity in syringe plus needle or syringe plus butterfly together never exceeded the 9% limit. Furthermore, in a pilot study we measured the remaining radioactivity in the vial; here, too, we found no more than 14% of total radioactivity. These findings indicate that total retention of radioactivity during elution and application of ^99mTc-tetrofosmin and ^99mTc-furifosmin with material used in our setting does not approach relevant amounts. Received 6 May and in revised form 19 May 1998     

Technetium-99m tetrofosmin and technetium-99m sestamibi imaging of multiple metastases from differentiated thyroid carcinoma

A 79-year-old male with follicular thyroid carcinoma metastasizing to the lung, bone and lymph nodes was subjected to whole-body scintigraphy using technetium-99m tetrofosmin and^99mTc-sestamibi. Both agents delineated the metastatic lesions and the two image qualities were comparable. We believe that^99mTc-tetrofosmin and^99mTc-sestamibi images may be helpful in localizing metastatic foci and substitute for thallium-201 in the follow-up of patients with differentiated thyroid carcinoma.     

Technetium-99m tetrofosmin uptake in lung cancer: Comparison with thallium-201

Technetium-99m tetrofosmin and thallium-201 lung SPECT imaging were performed in a patient with adenocarcinoma of the lung. Significant activities in the lung lesion were clearly depicted on both technetium-99m tetrofosmin and thallium-201 SPECT imaging. The early uptake, delayed uptake ratios and retention indices of the tumor were 2.75, 2.39 and ?13.1 for thallium-201 imaging and 3.09, 2.27 and ?26.5 for technetium-99m tetrofosmin imaging, respectively. This preliminary report suggests that technetium-99m tetrofosmin may have potential as a tumor imaging agent.     

Comparison of techniques for thallium-201-technetium-99m parathyroid imaging

It is impracticable to compare the variety of techniques advocated for thallium-technetium (Tl-Tc) subtraction parathyroid imaging by repeated studies in patients. We therefore carried out studies using a phantom assembly to simulate thyroid and parathyroid in the neck, containing activities of 99Tcm and 201Tl similar to those likely to be present in patient imaging. An initial study of imaging protocol confirmed that correction for scatter from 99Tcm in the 201Tl window usefully improved the image. After making a preliminary selection of gamma cameras and collimators it was found that the GE Maxicamera 400T just visualized the 0.3 g "parathyroid" in a 5 min image with the pinhole collimator and 6 mm insert (A). It performed slightly less well with the HR converging collimator (B) and only marginally better with the 4 mm insert (C), but this is unduly slow unless it is placed close enough to limit the field of view unacceptably. The Siemens Orbiter 75 ZLC with special thyroid collimator (D) gave results similar to (A), is convenient for positioning the patient and is very suitable for parathyroid imaging.     

Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy

Myocardial perfusion in ten normal volunteers and 20 patients with coronary artery disease documented by recent coronary arteriography was studied with 99mTc-labeled SQ30217 and 201TI. Plantar 201TI imaging followed standard treadmill exercise and planar SQ30217 imaging followed upright bicycle exercise, performed to angina, or the same double product achieved on the treadmill test. Upright anterior, 30 degrees left anterior oblique, and 60 degrees left anterior oblique images were obtained for 3, 6, and 9 min, respectively, starting 2 min after injection of 15 mCi of 99mTc SQ30217. A second 15-mCi dose was injected at rest approximately 2 hr later, and the same imaging protocol was followed. No adverse reactions or laboratory abnormalities attributable to SQ30217 were observed. All scans on the normal volunteers were interpreted as normal. Qualitative readings of both tests were equally sensitive for detecting patients with coronary disease (SQ30217 - 16/20, TI - 17/20, p = NS) and identifying abnormal vessels (SQ30217 - 19/45, TI - 21/45, p = NS). Both agents were falsely positive in 1/15 vessels. Ten vascular regions showed persistent abnormalities on resting SQ30217 scans; eight of these were distal to stenoses of at least 90% and three were also abnormal on thallium redistribution images. Hepatic uptake of SQ30217 obscured inferoapical segments in some views in 14/20 patients but did not interfere with abnormal vessel identification.     

Disappointing results with Tc-99m tetrofosmin for detecting medullary thyroid carcinoma metastases comparison with Tc-99m VDMSA and TI-201.

PURPOSE: This prospective study assessed the detectability of metastatic lesions by Tc-99m tetrofosmin in medullary thyroid carcinoma and to compare the results with Tc-99m penta dimercapto succinic acid (VDMSA) and TI-201. METHODS: A prospective study was performed on 24 patients (10 men, 14 women; ages 23 to 76 years) with medullary thyroid carcinoma after total thyroidectomy. Five cases were sporadic and 19 were familial. After the injection of 740 MBq (20 mCi) tetrofosmin, 740 MBq (20 mCi) VDMSA and 74 MBq (20 mCi) TI-201, whole-body scans and 5-minute static images of the head, neck, chest, abdomen and pelvis were obtained. All scintigraphic studies were compared with calcitonin levels, radiologic findings, histopathologic results, and clinical follow-up. RESULTS: Thirty-four metastatic sites were detected in 12 patients on the basis clinical, radiologic, and histopathologic findings. Patients were divided into three groups according to the calcitonin levels and scintigraphic findings. Group 1 consisted of patients with elevated calcitonin levels and positive scintigraphic findings. Among 34 metastatic sites, 30 could be detected with VDMSA. Only 21 and 20 metastatic sites could be visualized with TI-201 and tetrofosmin, respectively. All 30 lesions showed intense VDMSA uptake but only faint or no uptake with TI-201 and tetrofosmin. Patients in group 2 were accepted to have micrometastases. In this group, calcitonin was minimally elevated, and the results of all three scintigraphs were negative. Group 3 included patients with true-negative results. All patients had normal calcitonin levels and negative results of scintigraphic studies. CONCLUSIONS: Tetrofosmin has no role in the detection of medullary thyroid carcinoma metastases. These results show that VDMSA is clearly superior to TI-201 and tetrofosmin in the follow-up of patients with medullary thyroid carcinoma.     

Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology

A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for 201Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine needle aspiration biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR-ER) x 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and < or =1.42, 1.24 and 5 for 201Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%, 94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and 201Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules.     

Comparison of technetium-99m-MIBI and thallium-201-chloride uptake in primary thyroid lymphoma.

A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2-methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl-chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma.     

Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology

A comparative prospective study of technetium-99m methoxyisobutylisonitrile (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for ²⁰¹Tl) imaging in the differentiation of thyroid lesions is presented. Forty patients with cold thyroid nodules visualised on ^99mTc-pertechnetate scan and with dyskaryotic or atypical epithelial cells verified by fine-needle aspiration biopsy underwent MIBI and ²⁰¹Tl scintigraphy at 3-day intervals. Subsequent thyroidectomies were carried out in all patients. Semiquantitative analysis was performed using a lesion to non-lesion ratio on early (ER) and delayed images (DR). Additionally, a retention index (RI) was calculated using the formula RI=(DR– ER) × 100/ER. The reproducibility of the method for the early and delayed measurements was tested by analysing intra- and inter-observer variability and repeatability coefficients. Histopathologically, the nodules were found to be well-differentiated thyroid cancer in 21 patients and benign in 19 patients. There was no significant difference in the ER between malignant and benign lesions for either ²⁰¹Tl or MIBI (P>0.05). However, for both agents significant differences were found between malignant and benign lesions with regard to DR (P<0.01 for ²⁰¹Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents). Statistical comparison of the two agents showed no significant differences (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A receiver operating characteristic analysis was performed to determine threshold levels for the differentiation of malignant from benign nodules. Following this analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and ≤1.42, 1.24 and 5 for ²⁰¹Tl were selected. Using these threshold levels, the sensitivity, specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI, 61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%, 47.3% and 67.5% for ER ²⁰¹Tl, 80.9%, 73.6% and 77.5% for DR ²⁰¹Tl, and 90.5%, 94.7% and 92.5% for RI ²⁰¹Tl. In conclusion, the DR for MIBI and ²⁰¹Tl is superior to the ER in detecting malignant nodules, and the RI for both MIBI and ²⁰¹Tl is more valuable than the DR in differentiating malignant from benign thyroid nodules. Received 24 October 1999 and in revised form 8 January 2000