Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. METHODS: Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. RESULTS: Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). CONCLUSION: Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.     

99m-Tc-MIBI SPECT parathyroid gland scintigraphy for the preoperative localization of small parathyroid gland adenomas

AIM: It was the of this study to assess the value of the 99mTc-MIBI scintigraphy in SPECT technique in the preoperative lateral location of small parathyroid adenoma (PTA). METHODS: 25 consecutive patients (8 male, 17 female, mean age 63 +/- 13 years) with the established diagnosis of primary hyperparathyroidism and non-diagnostic ultrasonography were scanned preoperatively. After a thyroid examination to exclude radionuclide accumulating thyroid adenoma, planar and tomographic images were acquired 20 min. and 120 min. after i.v. injection of 740 MBq 99mTc-MIBI using a 3 head gamma camera (Picker Prism 3000). The first 10 patients underwent an additional 201Tl/99mTc subtraction scintigraphy in a 2 days protocol. RESULTS: All patients had small, solitary PTA (< 1 g). 201Tl/99mTc subtraction scintigraphy (n = 10) showed only a sensitivity of 50%. Using planar MIBI-scintigraphy lateral location of PTA was possible in 18 cases (sensitivity: 72%). There was an increase in sensitivity up to 96% using the SPECT technique and the 3D display (volume-rendered reprojection). CONCLUSION: In contrast to 201Tl/99mTc subtraction scintigraphy, which showed only a low sensitivity, a reliable lateral location of small PTA was obtained using the tomographic 99mTc-MIBI scintigraphy. This method offers e.g. the possibility for the surgeon to perform an unilateral parathyroidectomy.     

Technetium-99m-MIBI and thallium-201 scintigraphy of primary lung cancer

We evaluated the usefulness of 99mTc-MIBI scintigraphy in primary lung cancer in comparison with 201Tl-chloride scintigraphy. METHODS: There were 45 patients with primary lung cancer. All patients underwent dual-isotope imaging with 201Tl-chloride and 99mTc-MIBI. Regions of interest were placed over the tumors (T) and contralateral normal lung tissue (N) on one coronal view in the SPECT, and T/N ratio and retention index were calculated. RESULTS: The positive rate was 98% in both the early and delayed images for 201Tl-chloride and 96% in the early and 89% in the delayed image for 99mTc-MIBI. Both early and delayed T/N ratios for 201Tl-chloride were higher than those for 99mTc-MIBI. There was no significant correlation between T/N ratio and histological type of tumor in both images. However, in both images, there was a tendency for the early and delayed ratios to increase as the tumor diameter became larger. The retention index of 201Tl-chloride was higher than that of 99mTc-MIBI. There were no significant differences in the retention index with respect to the histological type and tumor size. CONCLUSION: The results of this preliminary clinical study suggest that 99mTl-MIBI can depict primary lung cancer similar to 201Tl-chloride. However, T/N ratio and retention index of 99mTc-MIBI in the tumor areas are significantly lower compared with those of 201Tl-chloride.     

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: 0=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 201Tl 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.     

Technetium-99m tetrofosmin imaging in patients with subacute thyroiditis

We studied the significance of technetium-99m tetrofosmin scintigraphy in patients with subacute thyroiditis (SAT). Six patients with SAT, who had painful goitre with thyrotoxicosis, underwent 99mTc-pertechnetate scintigraphy and 99mTc-tetrofosmin imaging during the acute and recovery stages of SAT. The thyroid uptake ratio of tetrofosmin was compared with the clinical parameters associated with SAT. 99mTc-pertechnetate scintigraphy showed markedly reduced uptake in the thyroid during the acute stage of SAT, suggesting that the appropriate metabolic pathway is not functioning. Conversely, 99mTc-tetrofosmin images showed diffuse increased uptake in the thyroid region on early and delayed imaging. Tetrofosmin images in the acute stage and in the recovery stage of SAT showed different clearance curves for tetrofosmin uptake. The uptake ratio assessed as thyroid uptake/background (T/B) correlated with the serum C-reactive protein concentration. In conclusion, 99mTc-tetrofosmin uptake may reflect the inflammatory process associated with SAT, and thus this tracer may have potential as a marker of disease activity and severity.     

The relevance of somatostatin receptors in thyroid neoplasia

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).     

Preoperative evaluation of the chemosensitivity of breast cancer by means of double phase 99mTc-MIBI scintimammography

The chemosensitivity of breast cancer is important for its management, but it is difficult to evaluate preoperatively. Tc-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintimammography has been reported to indicate the expression of P-glycoprotein, which is one factor concerned with multidrug resistance. We developed a chemosensitivity assay by using surgical specimens to investigate whether 99mTc-MIBI scintimammography findings before the operation are related to chemosensitivity according to our assay. Fifteen patients with primary breast cancer were enrolled into the study. Early and delayed images were obtained at 10 and 120 minutes after intravenous injection of 99mTc-MIBI, respectively. Regions of interest were placed on the tumors and the contralateral healthy breasts in each patient to estimate 99mTc-MIBI uptake in the tumor, and retention indices were then calculated to assess the washout of 99mTc-MIBI. Chemosensitivity assay was performed by incubating surgical specimens with anticancer agents such as doxorubicin, epirubicin, pinorubicin, mitomycin C, cisplatin and 5-fluorouracil. 99mTc-MIBI washout on scintimammography was successfully related to inhibition ratios on chemosensitivity tests when compared with 99mTc-MIBI uptake by the tumor. In particular, high correlation coefficients were obtained between the retention index of 99mTc-MIBI and the inhibition ratios of doxorubicin (r = 0.75), epirubicin (r = 0.60) and pinorubicin (r = 0.62), but poor correlation was found for mitomycin C (r = 0.44) and cisplatin (r = 0.31). Our results indicate that the retention index of 99mTc-MIBI is closely correlated to chemosensitivity to anthracyclines, suggesting that double-phase scintimammography allows preoperative prediction of chemosensitivity of breast cancer.     

Accumulation of Tc-99m MIBI in breast lymphoma: comparison with Ga-67 citrate

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.     

Computerized simulation technology for clinical teaching and testing

Each of myocardial blood flow imaging agents has a potential usefulness as an agent for tumor scintigraphy. The tumor accumulation and washout of 99mTc-tetrofosmin and 99mTc-MIBI were comparatively studied using rabbits bearing VX-2 cancer. From seventeen to twenty days after the implantation of VX-2 cancer into the femoral region of seven rabbits, tumor to soft tissue accumulation ratio (T/S ratio) of each agent was calculated in early images (5 min after injection) and in late images (50 min after injection). Compared with 99mTc-tetrofosmin, the T/S ratio of 99mTc-MIBI was higher and, moreover, the washout was delayed. These results suggest that there is a difference in tumor accumulation property between these two agents.     

Preoperative localization of parathyroid lesions in hyperparathyroidism: relationship between technetium-99m-MIBI uptake and oxyphil cell content

The aim of this study was to assess the relationship between parathyroid oxyphil cell content and early or late phases of uptake of 99mTc-MIBI, a radioisotope preferentially retained in mitochondria-rich cells. METHODS: This study is a retrospective, single-blind analysis of all double-phase 99mTc-MIBI parathyroid scintigraphy studies performed before surgery in our institution between 1990 and 1995. A total of 18 parathyroid lesions in 14 patients were reviewed. This sample included 11 cases of primary hyperparathyroidism (8 adenomas, 1 adenocarcinoma and 2 hyperplasias) and 3 cases of tertiary hyperparathyroidism secondary to chronic renal failure. RESULTS: Uptake of 99mTc-MIBI in the early phase of scintigraphy was associated with larger parathyroid lesions (1.61 +/- 1.61 ml versus 0.33 +/- 0.27 ml; p < 0.02) and higher serum calcium levels (3.00 +/- 0.41 mM versus 2.67 +/- 0.14 mM; p < 0.02). More importantly, we found that a parathyroid oxyphil cell content greater than 25% was more often associated with a positive uptake of 99mTc-MIBI in the late phase of the test (positive late uptake in 78% of lesions with a high oxyphil cell content versus 33% in lesions with an oxyphil cell content between 1% and 25% and 0% in lesions with no oxyphil cells; p < 0.04). CONCLUSION: These findings suggest that the late retention of 99mTc-MIBI in double-phase scintigraphy is related to parathyroid oxyphil cell content.     

The neuropathy of Dejerine and Sottas: report of an Indian family

We report a case of metastatic insular carcinoma of the thyroid evaluated with 201TI, 99mTc-MIBI, 99mTc-(V)DMSA, 99mTc-MDP and 131I whole-body scans, which were obtained after total thyroidectomy. For the majority of lesions detected in the skeleton and soft tissue, 131I images were generally available, although most were visualized easier with 99mTc-(V)DMSA. Technetium-99m-MDP images were considered better than 99mTc-(V)DMSA images in showing bone lesions but not soft-tissue lesions. Both 201TI and 99mTc-MIBI scans provided sufficient advantage to exhibit neck and mediastinal metastases, but they did not surpass 99mTc-(V)DMSA in detecting abdominal or bony lesions. In this patient with various metastases from insular carcinoma of the thyroid, 99mTc-(V)DMSA seemed to be the tracer of choice for whole-body imaging.     

Technetium 99m tetrofosmin parathyroid imaging. Results with double-phase study and SPECT in primary and secondary hyperparathyroidism

RATIONALE AND OBJECTIVES: The aim of our study was to evaluate the sensitivity, specificity, and positive predictive value (PPV) of technetium 99m (99mTc) tetrofosmin double-phase scintigraphy and single-photon emission computer tomography (SPECT) in preoperative localization of parathyroid adenoma in case of primary and secondary hyperparathyroidism (HPT). METHODS: Sixty-eight consecutive patients biochemically or sonographically suspected of parathyroid adenoma were included in our study. Apart from biochemical analysis of serum calcium, phosphate, and intact parathyroid hormone, double-phase scintigraphy was performed in each patient 5 and 45 minutes after injection of 370 MBq 99mTc tetrofosmin, followed by SPECT imaging. In consciousness of the scintigraphic results, ultrasound of the neck was performed as well to exclude false-positive results due to thyroid adenomas. RESULTS: Depending on the results of the biochemical analysis in combination with the results of the scintigraphic and ultrasound examination, the patients were classified retrospectively into three groups: group A with primary HPT (n = 35), group B with secondary HPT (n = 13), and group C without any biochemical suspicion of primary or secondary HPT (n = 20). In group A, double-phase study localized 25 of 36 (69.2%) parathyroid adenomas (one double adenoma) as against 34 of 36 (94.4%) with SPECT. Nine adenomas could be visualized only by SPECT. The reason for nonvisualization on planar scans was suspected to be an ectopic location in 2 cases (retrotracheal dislocation, retrovascular dislocation), a maximal diameter less than 15 mm (9-13 mm) in 6 cases, and oxyphilic-cell-poor cellularity in 1 case. Four false-positive retention (3 thyroid adenomas and 1 papillary thyroid carcinoma) were observed. SPECT showed a sensitivity of 94.4%, a specificity of 85%, and a PPV of 91.9% in biochemically suspected primary HPT. In group B, planar scintigraphy demonstrated 12 hyperplastic glands in 5 of 13 patients, and SPECT demonstrated 20 hyperplastic parathyroid glands in 8 out of 13 patients, which corresponds to a sensitivity of 38% and 61.5%, respectively. CONCLUSIONS: Technetium 99m tetrofosmin seems to be a promising alternative tracer with similar capabilities to 99mTc sestamibi in localization of parathyroid adenoma. SPECT showed clear advantages in terms of sensitivity over planar scintigraphy and should be used at least in cases with poor or no uptake in double-phase study. In endemic goiter areas, ultrasound of the neck should be performed to exclude false positive retention in thyroid adenomas. Technetium 99m tetrofosmin, like 99mTc sestamibi, is not ideal for localization of hyperplastic glands in secondary hyperparathyroidism because of low sensitivity.     

Ectopic parathyroid adenoma. Two cases treated with video-assisted thoracoscopic surgery

In recurrent or persistent hyperparathyroidism, accurate location of the abnormal gland is essential before further surgery, but the variety of available imaging techniques suggests that no one procedure is universally reliable. We report two cases in which clear preoperative visualization of adenoma with double-phase 99mTc-MIBI scintigraphy and exact high-resolution CT location permitted successful minimally invasive surgery.     

Clinical value of scintigraphic tumor diagnosis by means of test substances with tumor affinity. 2. Gallium radioisotopes

Deriving from the principle of direct tumor visualization and the beginnings of positive imaging of malignant tumors, radiotracers with tumor affinity are distinguished by those with tumor-specific and non-specific uptake. With special regard to the tumor-specific localization of thyroid carcinomas using radioiodine (131J) and of osteoplastic bone tumors or metastases using 99m-labelled phosphate compounds, the tumor scintigraphy results mainly with radiopharmaceuticals possessing tumors affinity, however not a tumor-specific uptake. On the basis of experimental and clinical results Gallium-67, one of these tumor-seeking agents, has become most important tumor scintigraphy. The diagnostic possibilities and limitations in using Gallium-67 for tumor imaging are derived from: 1) the non-specific uptake of Gallium-67, 2) the diagnosis accuracy and its reasons, and 3) the determinant factor of viability of tumor affecting the Gallium-67 accummulation.     

Technetium-99m methoxyisobutylisonitrile single-photon emission tomography in hepatocellular carcinoma

Nine lesions in eight patients with hepatocellular carcinoma (HCC) were studied using single-photon emission tomography (SPET) and technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) to evaluate the pattern of uptake of 99mTc-MIBI in the lesions and the relation between the uptake pattern and the histopathology of HCC. All the lesions were diagnosed as HCC by percutaneous needle biopsy. Four of the nine lesions showed positive uptake of 99mTc-MIBI, while the other five showed negative uptake. All of the lesions which showed positive uptake were of the compact type. Of the five lesions that showed negative uptake, four were of the trabecular type while one was of the compact type. These results suggest that the patterns of 99mTc-MIBI accumulation in HCC are divided into positive and negative types and that these uptake patterns are associated with the tissue structure of HCC.     

Observation of live, attenuated hepatitis A vaccines in humans

In a patient with metastatic Hurthle cell carcinoma of the thyroid, a subgroup of follicular carcinoma, scintigraphy with pentavalent 99mTc-labeled dimercaptosuccinic acid (V)DMSA showed a significant uptake of the radiopharmaceutical in all tumor sites. We suggest that the accumulation of 99mTc-(V)DMSA within metastases of Hurthle cell thyroid tumor may have a useful role in the staging of these patients, especially when radioiodine fails to concentrate.     

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.     

Gallium-67 scintigraphy in lymphoma with bone involvement

Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium-99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment.     

In-111 monoclonal antibody versus Ga-67 citrate and Tc-99m SC subtraction in a patient with malignant melanoma

Gallium-67 is routinely used for follow-up of patients with malignant melanoma. However, its nonspecificity for melanoma and its high rate of false-positive results have always been a matter of concern. The authors describe a patient who encountered serious problems with the use of gallium. Because gallium is taken up well by the liver and by melanoma, results of gallium scintigraphy of the liver may appear normal even if there is metastatic disease. In this patient, results of gallium scintigraphy of the liver were negative for metastasis but revealed extrahepatic foci detected by the monoclonal antibody. Computed tomography showed areas of attenuation, revealing only a few intrahepatic tumors and no extrahepatic disease. Tc-99m SC revealed intrahepatic metastases, but no extra-hepatic metastases were seen. A monoclonal antibody (ZME-018) scintigram did reveal hepatic metastases along with probable small, extrahepatic, metastatic foci. Overall hepatic uptake of the monoclonal antibody was relatively low. An image subtraction algorithm was devised whereby the sulfur colloid image was subtracted from the gallium scintigram. The resultant image revealed both the intrahepatic and extrahepatic metastases seen on the ZME-018 images. It is likely that in the past many hepatic metastases have been missed because Tc-99m SC images have not been routinely used as part of melanoma management protocols. The uptake of the ZME-018 by the tumor was significantly higher than that of the normal liver, suggesting that ZME-018 labeled with the appropriate emitter may be an effective specific therapeutic tool in selected patients.