99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone

Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether a scan with 99mTc(V) DMSA could be used to identify patients for whom 188Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the 188Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for 188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between 99mTc and 188Re scans, and kidney-to-background ratios on 188Re scans were not higher than on 99mTc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188Re(V)DMSA treatment.     

Active inflammatory bowel disease: evaluation with 99mTc (V) DMSA scintigraphy

PURPOSE: To evaluate the use of pentavalent (V) technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) scintigraphy for the assessment of disease activity in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 99mTc (V) DMSA scintigraphy was performed in 76 patients. There were 36 patients with active IBD (11 with ulcerative colitis, 25 with Crohn disease), 28 patients with inactive disease (eight with ulcerative colitis, 20 with Crohn disease), and 12 patients with miscellaneous bowel disease. Sensitivity and specificity of 99mTc (V) DMSA scintigraphy in the diagnosis of IBD were calculated. In the group with active IBD, the disease activity and laboratory indices, as well as the endoscopic and histologic activity, were compared with the scanning activity index. Correlation coefficients between them were calculated with the Spearman rank test. RESULTS: 99mTc (V) DMSA scintigraphy had a 92% (33 of 36) sensitivity and an 86% (24 of 28) specificity in the detection of active IBD. A significant correlation between disease activity indices and scintigraphy score was demonstrated. Endoscopic and histologic activity was significantly correlated (P =.005 and.02, respectively, overall disease activity) with the scanning activity score. Of the group of patients with miscellaneous bowel disease, three with ischemic colitis had negative findings at scintigraphy. CONCLUSION: 99mTc (V) DMSA scintigraphy provides a noninvasive, practical, and accurate assessment of IBD activity.     

Detection by SPECT-CT scan with (99m)Tc-(V) DMSA of bone metastases in patient with medullary thyroid cancer

Multiple endocrine neoplasia syndrome, type 2B (MEN 2B), is a rare entity characterized by the presence of medullary thyroid cancer in 100% of the cases. The phenotype of this syndrome consists in the presence of marfanoid features and mucocutaneous neuromas. We describe the case of a male patient with MEN 2B syndrome who was diagnosed with medullary thyroid cancer after lung metastases was found. We analyze the role of DMSA-V and the new hybrid SPECT-CT scan systems in the extension study and monitoring of medullary thyroid cancer.     

Radiolabeling morpholinos with 90Y, 111In, 188Re and 99mTc

This laboratory is investigating morpholinos (MORF), a DNA analogue, for radiopharmaceutical applications. While we routinely radiolabel with (99m)Tc, we have now labeled MORFs with (111)In, (188)Re and (90)Y in anticipation of therapeutic studies. METHODS: A 25 mer MORF with a primary amine on the 3' equivalent end attached via a 10 member linker was conjugated with an isothiocyanate backbone derivative of DOTA (for labeling with (111)In and (90)Y) and with NHS-MAG(3) (for labeling with (188)Re and (99m)Tc). The in vitro stability of labeled MORFs were investigated and biodistribution was carried out in normal mice. RESULTS: As evident by size exclusion HPLC, ITLC and Sep-Pak analysis, all four radiolabeled MORFs were successfully radiolabeled. In each case, the labeled MORFs showed one sharp peak in HPLC that shifted completely to earlier retention times following addition of a polymer conjugated with the complementary MORF. In saline at room temperature and in 37 degrees C serum, the radioactivity profile of (111)In, (188)Re and (99m)Tc was unchanged over 48 h while over the same period, the (90)Y profile showed a pronounced lower molecular weight peak which did not shift and was shown to be most probably due to (90)Y-DOTA resulting from radiolysis. In addition, the recovery of (188)Re on HPLC decreased as samples aged probably due to oxidation to perrhenate which was retained by the HPLC column. The biodistributions at 1, 3 and 6 h in normal mice showed no important differences among all four labels with the exception that levels of radioactivity in stomach and thyroid were higher in the case of (188)Re due to in vivo oxidation of the radiolabel to perrhenate. CONCLUSIONS: When radiolabeled with DOTA, (90)Y-labeled MORF showed increased instabilities relative to that of (111)In and when radiolabeled with MAG(3), (188)Re showed in vitro and in vivo instabilities compared to (99m)Tc, but all labels were still largely intact after 48 h in saline or serum. Possibly because of the rapid clearance of MORFs, no important differences in biodistribution among (90)Y, (111)In and (99m)Tc labels were evident in normal mice. These strategies for labeling MORF with (90)Y and (188)Re therefore appear to be suitable for therapeutic applications although both show some evidence of instabilities.     

Technetium-99m (V) DMSA uptake in amyloidosis

Technetium-99m(V) DMSA scintigraphy was performed in two patients with pathologically confirmed amyloidosis associated with plasmacytoma. Significant uptake of the tracer was found in the deposition of amyloid. Technetium-99m(V) DMSA scintigraphy could be useful in determining the appropriate region of biopsy and in forecasting the prognosis of patient with plasmacytoma.     

A convenient method for the preparation of 99mTc(V)dimercaptosuccinic acid (99mTc(V)-DMSA)

Tc(IV)-DMSA for kidney scintigraphy has been prepared in acidic solution. Once the labeling is done in basic solution, upon addition of a small amount of NaHCO3, a mixture of 3-4 other DMSA-complexes is formed, presumably containing Tc(V). Kidney uptake in male adult rats of the 99mTc(V)-DMSA is 1.6% injected dose/g (4.9%/total organ) compared to 16.4% injected dose/g (resp. 50.3%/total organ) for 99mTc(IV)-DMSA.     

Positive imaging of cardiomyopathy with99mTc(V)-DMSA

A case of histologically proven dilated cardiomyopathy and a case of clinically diagnosed cardiomyopathy (cardiac amyloidosis was strongly suspected but was not confirmed) were examined with 99mTc(V)-dimercaptosuccinic acid (DMSA). 99mTc(V)-DMSA accumulation in the damaged myocardium was clearly demonstrated. These results suggested the possibility that 99mTc(V)-DMSA could be used as a positive agent for cardiomyopathy.     

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     

Tc-99m(V) DMSA uptake in cardiac amyloidosis.

Tc-99m(V) DMSA scintigraphy was performed on two patients with primary cardiac amyloidosis. Scintigraphy performed (after radionuclide administration) showed accumulation in the myocardium.     

Scintimammographic findings of in situ ductal breast carcinoma in a double-phase study with Tc-99m(V) DMSA and Tc-99m MIBI value of Tc-99m(V) DMSA

The authors present a case of in situ ductal carcinoma of the breast (DCIS) with no associated mass in a 46-year-old woman examined with Tc-99m MIBI and Tc-99m(V) DMSA scans, which were acquired in separate sessions 10 minutes and 60 minutes after injection. Histologic analysis revealed a small (<1 cm) infiltrating ductal carcinoma located within the DCIS. Mammography showed a cluster of microcalcifications on a very dense parenchymal background. Tc-99m(V) DMSA was characterized as positive for DCIS, especially in the delayed image. Tc-99m MIBI failed to identify the lesions previously noted. In conclusion, Tc-99m(V) DMSA scintimammography seems to have an advantage and could improve the detection of nonpalpable in situ breast carcinomas.     

A comparative study of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, ¹⁸⁸Re complexes with diastereomeric DMSA were prepared to compare the properties of ¹⁸⁸Re(V)-rac-DMSA with those of ¹⁸⁸Re(V)-meso-DMSA in in vitro and in vivo models.

Methods

rac-2,3-DMSA was synthesized and radiolabeled with ¹⁸⁸Re. The biodistribution and gamma camera imaging of ¹⁸⁸Re(V)-meso-DMSA and ¹⁸⁸Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines.

Results and conclusions

Both ¹⁸⁸Re(V)-meso-DMSA and ¹⁸⁸Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with ¹⁸⁸Re(V)-meso-DMSA, ¹⁸⁸Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. ¹⁸⁸Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas ¹⁸⁸Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of ¹⁸⁸Re(V)-rac-DMSA was 3.5 times higher than that of ¹⁸⁸Re(V)-meso-DMSA at 1 h (P<.01). Gamma camera images showed that ¹⁸⁸Re(V)-rac-DMSA was more selectively localized than ¹⁸⁸Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that ¹⁸⁸Re(V)-rac-DMSA may have better potential than ¹⁸⁸Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors.     

99mTc bone scanning agents--II. Adsorption of 99mTc(Sn)pyrophosphate complexes on the mineral phase of bone

The adsorption of pyrophosphate, tin-pyrophosphate and 99mTc(Sn)pyrophosphate on Ca3(PO4)2 was investigated at pH 4.0 and pH 7.4. All components were radioactively labeled. Tin and reduced technetium were in most cases almost completely bound. The adsorption of pyrophosphate, tin(II) and technetium-99m at pH 4.0 was higher than at pH 7.4. The presence of tin gave rise to an increase of the pyrophosphate adsorption that was much larger than can be accounted for by a stoichiometric adsorption of tin-pyrophosphate. It is concluded that tin and technetium are bound as negatively charged complexes with pyrophosphate. Finally it is argued that the fraction of the bone scanning agent that reaches the bone surface is adsorbed completely by the mineral phase.     

The role of Tc-99m (V) DMSA scintigraphy in the evaluation of superscan on bone scintigraphy

PURPOSE: This study evaluated the biodistribution of Tc-99m (V) DMSA in patients with superscans on bone imaging and defined its role in differentiating the underlying cause. METHODS: Nine patients (five with metastatic and four with metabolic bone disease) with classical superscans were entered into the study. All patients had the necessary radiologic and biochemical studies and a final diagnosis was reached accordingly. Tc-99m (V) DMSA scintigraphy was performed 1 week after Tc-99m MDP whole-body bone imaging. RESULTS: In four of five patients with widespread skeletal metastases, Tc-99m (V) DMSA scan showed diffusely increased bone uptake. In the remaining patient, the Tc-99m (V) DMSA scan showed a normal distribution pattern. All patients with metabolic bone disease had increased bone uptake on Tc-99m (V) DMSA scans. CONCLUSION: Tc-99m (V) DMSA shows increased bone uptake in patients having a superscan appearance in metastatic or metabolic bone disease. Tc-99m (V) DMSA imaging may play a role in the evaluation of patients with equivocal bone scan findings for a superscan.