Comparison of99mTc(V)-DMSA,201Tl and99mTc-MIBI imaging in the follow-up of patients with medullary carcinoma of the thyroid

Radionuclide scanning with tumour-seeking agents such as pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA], thallium-201 and technetium-99m sestamibi (MIBI) has been reported to be useful in the detection of medullary thyroid carcinoma (MTC). We undertook a study in 14 MTC patients to determine the comparative imaging potential of²⁰¹Tl, MIBI and^99mTc(V)-DMSA in the detection of recurrent or metastatic MTC. All patients underwent total thyroidectomy and had persistently elevated serum calcitonin levels after the surgery. Scintigraphic studies were carried out 20 min after the injection of 111 MBq of²⁰¹Tl or 555 MBq of MIBI and 2 h following the injection of 370 MBq of^99mTc(V)-DMSA. All scintigraphic findings were correlated with contemporaneous CT or MRI studies. CT, MRI and bone scans showed 42 (26 bone, 16 soft tissue) metastatic sites in 11 of the 14 patients. In the remaining three patients no lesions were detected during diagnostic evaluation.^99mTc(V)-DMSA showed all of the soft tissue metastases but could not show two bone lesions. On the other hand, MIBI imaging was false-negative in 22 (52%) sites and²⁰¹Tl was false-negative in 34 (80%) sites. Overall, lesion detection sensitivities for^99mTc(V)-DMSA, MIBI and²⁰¹Tl were 95%, 47% and 19% respectively. We conclude that^99mTc(V)-DMSA is clearly superior to MIBI and²⁰¹Tl in the follow-up of MTC patients.     

Clinical evaluation of 99mTc(V)-dimercapto succinic acid (DMSA) for imaging medullary carcinoma of thyroid and its metastasis

^99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12(80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of ^99mTc (V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of ^99mTc (V)-DMSA (64.9%). In addition, ^99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of ^99mTc (V)-DMSA concentration in soft tissue and bone metastasis was similar.Isopharm, Radiopharmaceutical Division, BARC, Bombay-400 705, India     

Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [¹¹¹In-DTPA-d-Phe¹]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [¹¹¹In-DTPA-d-Phe¹]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq ^99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [¹¹¹In-DTPA-d-Phe¹]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using ^99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for ^99mTc(V)-DMSA and [¹¹¹In-DTPA-d-Phe¹]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [^99mTc(V)-DMSA] and receptor ([¹¹¹In-DTPA-d-Phe¹]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither ^99mTc(V)-DMSA nor [¹¹¹In-DTPA-d-Phe¹]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC. Received 10 February and in revised form 20 May 1998     

99mTc(V)-DMSA and99mTc-MDP uptake and no67Ga-citrate uptake in a case of primary pulmonary leiomyosarcoma

Tumor scintigraphy with 67Ga-citrate, 99mTc(V)-DMSA and 99mTc-MDP were performed on a patient with rare primary pulmonary leiomyosarcoma. While 67Ga-citrate accumulation to the tumor was not recognized, 99mTc(V)-DMSA and 99mTc-MDP scintigraphy showed relatively intense localization of the tracers in the lesion, and were very useful in suggesting the characteristics of the tumor.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. ^99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO₃ solution in the presence of a small amout of reducing agent (SnCl₂). On the other hand, trivalent ^99mTc-DMSA [^99m-Tc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only ^99mTc(V)-DMSA revealed an area of intense accumulation.     

Solitary muscular sarcoidosis: CT,MRI, and scintigraphic characteristics

Scintigraphy using gallium-67 (⁶⁷Ga) citrate and penvaralent technetium-99m dimercaptosuccinic acid {[^99mTc(V)]DMSA} and other radiological examinations were performed in three patients with solitary muscular sarcoidosis who had tumor-like muscular lesions. Although distinction from other invasive soft tissue tumors was difficult using plain and enhanced computed tomography and magnetic resonance imaging, marked uptake of⁶⁷Ga and moderate uptake of [^99mTc(V)]DMSA were shown at the sites of granulomatous inflammatory lesions of sarcoidosis. Both⁶⁷Ga and [^99mTc(V)]DMSA scintigraphy could be of value in the diagnosis and detection of distribution of granulomas of sarcoidosis in the soft tissue and in determining the appropriate region for biopsy.     

Tc-citrate versus Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with ^99mTc with an efficiency of > 99%. The biodistribution of ^99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to ⁶⁷Ga-citrate. The max. concentration ratios were 4.61 ± 1.92 (3 h) for ^99mTc-citrate and 4.76 ± 2.04 (4h) for ⁶⁷Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of ^99mTc-citrate showed increased activity involving the synovium. The max. knee ratio was 3.19 ± 1.29 (3 h) and 6.47 ± 3.71 (24 h) for ^99mTc- and ⁶⁷Ga-citrate, respectively. The blood clearance curve of ^99mTc-citrate in rabbits was biexponential with a fast ( ) and a slow ( ) component, compared to mono-exponential clearance of ⁶⁷Ga-citrate ( ). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 ± 0.81 and 4.95 ± 2.56 for ^99mTc-citrate and ^99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that ^99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to ⁶⁷Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Pitfalls in scintigraphic detection of neuroendocrine tumours

We report 4 cases of abnormal results using iodine-123 metaiodobenzylguanidine (¹²³I-mIBG) or technetium-99m (V) dimercaptosuccinic acid (^99mTc(V)-DMSA) scintigraphy in the diagnosis and follow-up of presumed neuroendocrine tumours. The present series consisted of 2 false-positive cases (1 adenomatous polyp of the caecum with mIBG and 1 follicular adenoma of the thyroid with DMSA) and 2 cases of anomalous uptake of (V)-DMSA in a non-neuroendocrine tissue.Workin part presented at the International Congress G.R.A.D.O. 4 Rome, 10–11 May 1991 Offprint requests to: L. Feggi, 1, via Poledrelli, I-44100 Ferrara, Italy     

Comparison of delayed hepatobiliary imaging using 99mTc-Sn-N-pyridoxyl-5-methyltryptophan and 67Ga-citrate imaging for diagnosis of hepatocellular carcinoma

Images were obtained both with a biliary agent, ^99mTc-Sn-N-pyridoxyl-5-methyltryptophan (^99mTc-PMT), and with ⁶⁷Ga-citrate in 40 cases of hepatocellular carcinoma and in 43 cases of other hepatic diseases and results were compared. Positive results were obtained by delayed ^99mTc-PMT imaging in 25 (63%) of 40 cases of hepatoma: the hepatic tumor showed increased uptake in 18 cases (45%) and equilibrated uptake in 7 cases (18%). Positive ⁶⁷Ga-citrate imaging was found in 28 (70%) of the 40 cases of hepatoma: increased uptake was seen in 24 cases (60%) and equilibrated uptake in 4 cases (10%). Of 15 cases of hepatoma giving negative results in the ^99mTc-PMT study, 7 cases (47%) took up ⁶⁷Ga-citrate, and 6 of these showed increased ⁶⁷Ga-citrate uptake by the hepatic tumors. A certain relation existed between the degree of histological differentiation of hepatomas and the intensity of ^99mTc-PMT uptake by those tumors, while such a histological correlation was denied for ⁶⁷Ga-citrate uptake by the tumors. Delayed ^99mTc-PMT imaging is preferable to ⁶⁷Ga-citrate imaging for increasing the specificity of diagnosis of hepatoma. ⁶⁷Ga-citrate should be used in those cases that do not give positive results with ^99mTc-PMT.     

Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours

Scintigraphy using [¹¹¹In-DTPA-d-Phe¹]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [^99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and ^99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of ¹⁸F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative acitivity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas ¹⁸F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional ¹⁸F-FDG PET should be performed only if SS-R or DNS is negative. Received 8 July and in revised form 19 September 1997     

The value of gallium-67 and thallium-201 whole-body and single-photon emission tomography images in dialysis-related β2-microglobulin amyloid

The aim of this study was to investigate the value of gallium-67 and thallium-201 whole-body and single-photon emission tomography (SPET) images in long-term dialysis patients in whom dialysis-related β₂-microglobulin amyloid (β₂-MA) was clinically suspected. Twenty-three patients who had received dialysis for at least 10 years were included in the study. A technetium-99m methylene diphosphonate (MDP) whole-body scan was performed in all of the patients. If there was any MDP accumulation in the articular and/or peri-articular region, ⁶⁷Ga and ²⁰¹Tl whole-body and SPET images were then acquired. If any ⁶⁷Ga and/or ²⁰¹Tl uptake was observed, a CT-guided biopsy was done. In those patients who had articular and/or peri-articular uptake of ^99mTc MDP, ⁶⁷Ga and/or ²⁰¹Tl and who were pathologically proven to have β₂-MA, ^99mTc MDP, ⁶⁷Ga and ²⁰¹Tl whole-body scans and SPET were carried out again, both 3 months and 1 year after initiation of treatment. This served to evaluate the therapeutic effect and allowed comparison with the clinical findings. Of the 23 patients, eight had abnormal ^99mTc MDP uptake. Among these eight, six had intense ^99mTc MDP, ⁶⁷Ga and ²⁰¹Tl uptake in the articular and peri-articular regions before medication. Three months after the start of treatment, there were very marked decreases in uptake on both the ⁶⁷Ga and ²⁰¹Tl scans but less obvious changes in uptake of ^99mTc-MDP. In comparison with the other clinical manifestations such as limitation in range of motion, the more the painful disability improved, the less was the uptake on both ⁶⁷Ga and ²⁰¹Tl scans. There were virtually no differences in uptake pattern between the three scans of each radiopharmaceutical obtained for each patient in both 3 months and 1 year after initial of treatment. It is concluded that ^99mTc-MDP whole-body bone scan can both detect active and pre-existing inactive deposits of β₂-MA. ⁶⁷Ga and ²⁰¹Tl scans are helpful to differentiate active from inactive deposits of β₂-MA and to evaluate the therapeutic effect on these patients. SPET images are usually needed to distinguish articular and peri-articular lesions from bone lesions. Received 19 May and in revised form 9 August 1999     

Scintigraphic evaluation of aggressive fibromatosis

Despite its benign microscopic appearance, aggressive fibromatosis has potential to recur and infiltrate neighboring tissues. Therefore, it is necessary to determine the exact extent before therapy. In the present study, 11 cases of aggressive fibromatosis were examined scintigraphically using [99mTc(V)]dimercaptosuccinic acid (11 cases) and 67Ga-citrate (7 cases). Technetium-99m-(V)-dimercaptosuccinic acid demonstrated all lesions, while 67Ga-citrate detected 57% of the cases.     

Preparation and evaluation of 99mTc(V)-DMSA complex: Studies in medullary carcinoma of thyroid

Consequent to the promising results reported with ^99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways:-(i) from freshly prepared reagents, (ii) through the use of a two component kit and (iii) use of the standard renal DMSA kit by a modified recipe. The ^99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

Influence of Pi3-K and PKC activity on 99mTc-(V)-DMSA uptake: correlation with tumour aggressiveness in an in vitro malignant glioblastoma cell line model

Purpose Intensive proliferation and a high degree of migration and invasion are characteristic features of malignant glioblastomas, associated with a poor prognosis. Phosphatidylinositol-3-kinase (Pi3-K) and protein kinase C (PKC) are two phosphorylated proteins involved in glioblastoma cell progression. Phosphorylated focal adhesion protein kinase (FAK) has also been reported to be involved in tumour progression. In a recent study, we demonstrated a correlation between phosphorylated FAK, proliferation rate and ^99mTc-(V)-dimercaptosuccinate [(V)-DMSA] uptake. We hypothesised that ^99mTc-(V)-DMSA could be a potential imaging agent to evaluate glioblastoma aggressiveness. The aim of the present study was to assess the relationship between ^99mTc-(V)-DMSA incorporation rate and modulation of Pi3-K and PKC activity.Methods Proliferation, migration and invasion capacities in the presence of protein kinase modulators—staurosporine (PKC inhibitor), 4-phorbol 12-myristate 13-acetate (PMA; PKC activator) and LY294002 (Pi3-K inhibitor)—were correlated with ^99mTc-(V)-DMSA cell accumulation in an in vitro model of several malignant glioma cells: G111 (grade II), U-87-MG (grade III) and G152 (grade IV).Results In all cell lines tested, LY294002 and staurosporine treatment inhibited cell proliferation, migration and invasion. In contrast, treatment with PMA stimulated tumour aggressiveness. ^99mTc-(V)-DMSA uptake was strongly correlated with the % of cellular proliferation (r=0.8462) and the % of cellular migration (r=0.9081), and to a lesser extent with the % of cellular invasion (r=0.7761).Conclusion Our results clearly demonstrated that ^99mTc-(V)-DMSA reflects Pi3-K and PKC activity and is correlated with tumour aggressiveness. ^99mTc-(V)-DMSA could be a reliable in vivo marker providing additional information on the biological status of malignant glioblastoma.     

Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct

The clinical evaluation of thyroid imaging with^99mTc,²⁰¹T1, and⁶⁷Ga in the uncommon, but potentially serious, disorder of acute suppurative thyroiditis (AST) with abscess formation due to infection from a persistent thyroglossal duct is reported. The^99mTc image showed functioning areas of the diseased thyroid gland and the²⁰¹Tl image demonstrated abscess formation in the thyroid gland of this patient. In addition, marked⁶⁷Ga accumulation was demonstrated in a wide area covering not only the area of the thyroid gland involved, but also associated circumferential inflammatory lesions in a patient with AST. The net thyroid uptake of⁶⁷Ga at 72 hours was calculated to be 13.8% of the injected dose.     

Clinical evaluation of tumour imaging using 99Tc(V)m dimercaptosuccinic acid, a new tumour-seeking agent

Considering the favourable nuclear properties of 99Tcm over 67Ga, we have developed a new tumour-seeking agent, 99Tc(V)m dimercaptosuccinic acid (Tc(V)-DMSA). In order to evaluate the clinical usefulness of Tc(V)-DMSA scintigraphies, 492 patients were studied with Tc(V)-DMSA, and in some cases, where possible, the results were compared with conventional 67Ga citrate scintigraphies. There was a high degree of usefulness of Tc(V)-DMSA in patients with head and neck tumours, medullary thyroid carcinomas and soft tissue tumours. But in patients with carcinomas of the lung, liver and gastrointestinal tract, malignant melanoma and lymphoma, Tc(V)-DMSA was of no or little use.     

Analogy between tumor uptake of technetium(V)-99m dimercaptosuccinic acid (DMSA) and technetium-99m-MDP

Sixty patients with a variety of malignant tumors were examined with Tc-99m(V) dimercaptosuccinic acid (DMSA) prepared by modification of a commercially available DMSA kit. Significant uptake of Tc-99m(V)-DMSA was observed in a number of tumors, offering additional clinically useful information. In the majority of cases in this study, however, the benefit of the Tc-99m(V)-DMSA image was limited because of low sensitivity. The most striking observation was the similarity between the tumor concentration of Tc-99m(V)-DMSA and the Tc-99m-MDP uptake in the tumor on the regular bone image. Therefore, patients with Tc-99m-MDP uptake in nonosseous tumor sites on the bone scan may be suitable candidates for tumor imaging with Tc-99m(V)-DMSA.     

Oxygen bubbling can improve the labelling of pentavalent technetium-99m dimercaptosuccinic acid

It has previously been reported that almost all of the trivalent technetium-99m dimercaptosuccinic acid (^99mTc (III) DMSA) present in the labelling product of pentavalent technetium-99m DMSA (^99mTc (V) DMSA) can be changed into^99mTc (V) DMSA by bubbling with pure oxygen. We therefore performed studies in animals (mice) and humans to investigate the effect of such oxygen bubbling on the labelling efficiency of and on the renal uptake of^99mTc. The method of labelling of^99mTc (V) DMSA was that of Hirano. It was found that oxygen bubbling oxidized the contaminated^99mTc (III) DMSA into^99mTc (V) DMSA in vitro and decreased the uptake of radioactivity in the kidney in both animals and humans.