A comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans

Being aware of the ideal nuclear properties of Tc-99m, our interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studies with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.     

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.     

The role of Tc-99m (V) DMSA scintigraphy in the diagnosis and follow-up of lung cancer lesions

Objective To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). Methods Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. Results Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. Conclusions Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.     

Tc-99m(V) DMSA imaging. A new approach to studying metastases from breast carcinoma.

Combined Tc-99m MDP skeletal imaging and Tc-99m(V) DMSA whole body scans to detect metastases were performed during the follow-up of 30 patients who underwent surgery for breast carcinoma. Eight patients had normal Tc-99m MDP and Tc-99m(V) DMSA scans and were declared free of metastatic disease, further confirmed by no change in symptomatology over a 1-year follow-up period. Twenty-two patients had positive Tc-99m MDP scans with varied skeletal involvement. Tc-99m(V) DMSA scans showed matched areas of increased radiotracer concentration in bony metastases in 20 of these patients. Tc-99m(V) DMSA concentration was not seen in traumatic vertebral collapse or in coexistent osteoarthritic disease in vertebral metastatic involvement. Interestingly, Tc-99m(V) DMSA showed increased concentration in brain and liver metastases. Pentavalent Tc-99m(V) DMSA appears useful for detecting skeletal and soft-tissue metastases in breast carcinoma, and can improve the specificity of Tc-99m MDP bone scans in screening for bone metastases.     

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.     

Tc-99m(V)-DMSA in wound infection after closure of an ileostomy

We present a 71-year-old man who underwent closure of an ileostomy and had a fever seven days post surgery. Both Tc-99m(V)-dimercaptosuccinic acid (DMSA) and gallium-67 citrate scans showed increased tracer accumulation in the right lower quadrant of the abdomen. Tc-99m(V)-DMSA scintigraphy can be a rapid alternative tool in the detection of wound infection in patients after ileostomy closure.     

Pentavalent technetium-99m DMSA uptake in pseudofractures of osteomalacia

Tc-99m MDP and Tc-99m (V) DMSA images are described from a 49-year-old woman with chronic renal insufficiency complicated by osteomalacia. Clinical, biochemical, and radiologic bone profiles were compatible with osteomalacia. Osteomalacia is a condition associated with disorders in which mineralization of the organic matrix is defective. All bone lesions visualized with Tc-99m MDP also showed increased uptake of Tc-99m (V) DMSA. Tc-99m (V) DMSA accumulation has been reported in many malignant and some benign conditions. Pseudofractures in osteomalacia could be included in the spectrum of benign lesions that accumulate Tc-99m (V) DMSA.     

The role of 99mTc(V)-DMSA scan as compared to 99mTc-MDP and CT scans in imaging the primary tumor and metastases of osteosarcoma

The oncophilic complex of technetium-99m labeled pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) has been successfully used for the detection of primary and metastatic medullary thyroid cancer and for imaging various soft tissue tumors like lung, brain and prostate cancer. In this article, the role of 99mTc(V)-DMSA in the diagnosis of the primary tumor and metastases of osteosarcoma patients as compared to the 99mTc-MDP scan and the CT scan was studied. Twenty-eight patients with bone disease were referred to the Nuclear Medicine Department of Saint Savas Oncology Hospital in Athens from the Orthopedics Department of the same Hospital. From them, 18 (Group A) had osteosarcoma, 7 (Group B) osteomyelitis and 3 (Group C) bone fractures. The final diagnosis was made after fine needle aspiration biopsy. All patients were subjected to the 99mTc(V)-DMSA scan, the standard bone scan (99mTc-MDP) and CT scan. Group A patients showed a selective uptake of 99mTc(V)-DMSA in the primary tumor region. No abnormal 99mTc(V)-DMSA uptake was observed in the patients of Groups B and C. The 99mTc(V)-DMSA scan was found to be superior to the 99mTc-MDP and the CT scans in identifying metastases of osteosarcoma. Sensitivity was 100%, 86% and 98% respectively.     

Comparison of In-111 octreotide and Tc-99m (V) DMSA scintigraphy in the detection of medullary thyroid tumor foci in patients with elevated levels of tumor markers after surgery.

PURPOSE: In this retrospective study, the authors evaluated the utility of In-111 octreotide (OctreoScan) and Tc-99m (V) DMSA scintigraphy for the localization of recurrent metastatic tumor foci in patients with medullary thyroid cancer (MTC) and compared the findings with those of conventional radiologic imaging methods. METHODS: The scintigraphic images were compared with computed tomography (CT) and magnetic resonance imaging (MRI) and ultrasonography (US) in 14 patients (8 men, 6 women; age range, 22 to 74 years) with elevated calcitonin and carcinoembryonic antigen levels after total thyroidectomy. All scintigraphic image findings were evaluated qualitatively as mild uptake (+) and moderate to marked uptake (++). RESULTS: In-111 octreotide may be superior to Tc-99m (V) DMSA for the detection of tumor foci of patients with MTC on a patient basis (78.5% versus 57.1%) and on a lesion basis (44.1% versus 30.2%). The sensitivity rate for In-111 octreotide (78.5%) was also similar to that of CT and MRI on a patient basis. Conversely, the combined use of Tc-99m (V) DMSA and In-111 octreotide revealed the best sensitivity rate (85.7%) on a patient basis, whereas the combined use of CT and MRI showed the best sensitivity rate (81.3%) on a lesion basis. CONCLUSIONS: These findings suggest that In-111 octreotide is superior to Tc-99m (V) DMSA and has a similar sensitivity rate to CT and MRI for the diagnosis of recurrent or metastatic MTC. Although the combined use of In-111 octreotide and Tc-99m (V) DMSA was most sensitive, the combined use of CT and MRI with radionuclide imaging methods may better detect more metastatic tumor foci.     

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.     

Evaluation of stannous oxidation in the preparation of ultrahigh-purity 99m Tc(V)-DMSA

It has been shown previously that renal kit, trivalent technetium-99m dimercaptosuccinic acid [99mTc(III)-DMSA], can be transformed into tumour imaging agent, pentavalent technetium-99m DMSA [99mTc(V)-DMSA], by adding sodium bicarbonate (NaHCO3) and subsequently bubbling with oxygen. However, the purity of this pentavalent preparation was reported to be in the range 83-94% at best. In this study, the preparation of ultrahigh-purity 99mTc(V)-DMSA is described, and the role of stannous oxidation in the conversion of 99mTc(III)-DMSA to 99mTc(V)-DMSA is evaluated in order to understand the underlying mechanism. The results show that controlled oxygen bubbling increases the 99mTc(V)-DMSA levels, with a concomitant decrease in the 99mTc(III)-DMSA levels, in a time-dependent pattern. The purity of the pentavalent DMSA is shown to be consistently very high (>99%), as estimated by chromatography, and this correlates very well with the minimal or no renal uptake of this compound in patient studies.     

Increased bone marrow uptake on Tc-99m DMSA scintigraphy in a patient with renal osteodystrophy

A 16-year-old male patient was evaluated with Tc-99m Diethylenetriamine-pentaacetic acid (DTPA) and Tc-99m 2–3 Dimercaptosuccinic acid (DMSA) scintigraphy for renal failure secondary to renal calculi. The uptake in the renal cortex was significantly decreased both on DMSA and DTPA studies. Uptake calculation on DMSA scintigraphy in the kidneys disclosed values of less than 5 %. The activity in the liver and bone was significantly increased. A bone scan performed with Tc-99m methylene diphosphonate (MDP) revealed increased bone uptake with decreased soft tissue activity. Findings on bone scan were compatible with super scan, most likely due to renal osteodystrophy. This case illustrates the altered biodistribution of Tc-99m DMSA and a shift of the radiopharmaceutical to the bone marrow which is mot likely related to colloid formation due to changes in mineral balance in patients with renal failure.     

Tc-99m pentavalent DMSA scintigraphy in myelofibrosis detection

In a 62-year-old man with medullary carcinoma of the thyroid, a postoperative Tc-99m dimercaptosuccinic acid [(V) DMSA] study was requested. In the Tc-99m (V) DMSA scan. no abnormalities, indicating local recurrence or metastatic disease, were observed. However, there was increased uptake in the spleen and liver and significantly diffusely increased uptake in the bone marrow. The patient also had a history of myelofibrosis and these findings appear to have been the result of this pathology.     

Pathologic hepatic Tc-99m-MDP uptake in polyostotic fibrous dysplasia

Fibrous dysplasia of bone is a congenital, sporadic developmental disorder characterized by immature fibrous connective tissue and bone deformities. Hepatic Tc-99m-MDP uptake is a rare, serendipitous finding during bone scanning studies. The present patient was a 25-year-old male who had severe polyostotic fibrous dysplasia. On Tc-99m-MDP (methylene diphosphonate) bone scintigraphy, increased activity accumulations were seen on multiple ribs, vertebrae and base of the cranium. In addition, diffuse increased pathologic uptake of Tc-99m-MDP in the liver was shown. Intravenous pamidronate was administered monthly for two months. In the third week of the last administration Tc-99m-MDP bone scintigraphy was performed again, but despite sustained bone involvement, pathologic hepatic uptake was not seen on the scan. We thought that pathologic hepatic Tc-99m-MDP accumulation, may be related to the formation and aggregation of calcium oxalate and phosphate crystals which improved with pamidromat treatment.     

Using technetium-99m (V) dimercaptosuccinic acid to detect malignancies from single solid masses in the lungs

Fifty patients (43 male,7 female, age 31–77 years) with single solid masses in their lungs based on the findings of a chest X-radiograph [40 malignancies: 5 small cell carcinoma (Ca), 17 epidermoid Ca, 12 adeno Ca, 6 undifferentiated large cell Ca] and 10 benign lesions underwent technetium-99m (V) dimercaptosuccinic acid [^99m-(V)DMSA] scans to evaluate the usefulness of ^99mTc-(V)DMSA in the detection of lung Ca with different cell types and benign lesions. Only 43% (17/40) of the malignancies in the lungs were detected by ^99mTc-(V)DMSA, including 29% (5/17) epidermoid Ca, 50% (6/12) adeno Ca and 17% (1/6) undifferentiated large cell Ca of the lungs. However, all 5 cases of small cell Ca and 11 cases combined with bone metastasis were revealed by ^99mTc-(V)DMSA. In addition, 3 of the 10 benign lesions (2 organizing pneumonias, 1 benign tumor) presented with an uptake of ^99mTc-(V)DMSA. The diagnostic sensitivity, specificity and accuracy were 43%, 70% and 48%, respectively, in differentiating malignant from benign lesions for the single solid mass in the lungs. In conclusion, ^99mTc-(V)DMSA is of little or no use in the differentiation of lung Ca from single solid masses in the lungs. Correspondence to: C.H. Kao     

Novel tumortropic ester derivatives of 99mTc(V) mesodimercapto succinic acid with low affinity for bone tissue

Starting from our previous finding that 99mTc(V) dimercaptosuccinic acid (99mTc(V)-DMSA), a useful agent for the localization of osteosarcoma and bone metastases, loses its bone affinity when one ester group is introduced into the complex we studied the impact of esterification in more detail. This paper reports on the evaluation of various ester complexes of 99mTc(V)-DMSA in rats and tumour-bearing nude mice with regard to their tumour retention and improvement of the tumour to tissue ratios. The distribution patterns of the complexes [99mTcO(DMSA)2]- (A), [99mTcO(DMSA/DMSEt)]- (B) and [99mTcO(DMSEt)2]- (C) are gradually changed with the number of ester groups in the anionic complex. However, the asymmetric diester complex [99mTcO(DMSA/DMSEt2)]- (D) is very slowly cleared, especially from the blood of nude mice. Moreover, this complex differs significantly from the symmetrical complex C in its elimination behaviour from the liver and kidneys. The tumour uptake is maintained with complexes that contain one or two non-hydrolysable ester functions. Preliminary biodistribution studies of the monoethyl and diethyl ester complexes B, C and D in comparison with A in tumour-bearing nude mice showed similar uptake into the human squamous cell carcinoma (FaDu) as well as into the human colonic cell carcinoma (HT29) of nude mice. The low bone accumulation of B, C and D results in excellent tumour-to-bone ratios, e.g., approx. 3:1 for the ester complex B compared to approx. 1:2 for complex A. Differences were observed in the accumulation and elimination behaviour of the complexes A and B in various bone structures of rats. The age-dependent uptake of A and B was compared in long bone (femur) and in cranial bone of rats. The results suggest that 99mTc(V)-DMSA complexes that contain a functional ester, and their 188Re analogues, may be superior to 99mTc(V)/188Re(V)-DMSA in diagnostic and therapeutic nuclear medicine.     

Uptake of pentavalent technetium-99m dimercaptosuccinic acid in idiopathic synovial chondromatosis

We reported two Tc-99m(V) DMSA scintigrams in patients with idiopathic synovial chondromatosis which affected the metacarpo-phalangeal joint and shoulder joint. Tc-99m(V) DMS A accumulated markedly and diffusely in the tumor. Tc-99m(V) DMSA scintigraphy would be valuable for deciding the optimal site for biopsy.     

^99mTc（V）—DMSA骨显像诊断骨转移瘤的临床价值

目的：评价99mTc（V）－DMSA显像在骨转移瘤诊断中的意义。材料和方法：对91例疑骨转移瘤患者行99mTc（V）DMSA全身显像，并与99mTc-MDP全身骨显像及其它检查对比。结果：74例证实存在骨转移瘤者，99mTc．MDP骨显像均显示异常放射性浓聚，99mTc（V）-DMSA显像72例显示了与99mTc-MDP显像某些相同部位的放射性浓聚，2例99mTc（V）DMSA显像阴性。17例骨良性病变，99mTc－MDP骨显像显示轻度异常放射性浓聚，而99mTc（V）-DMSA显像却未见异常的放射性浓聚。结论：99mTc（V）－DMSA诊断骨转移瘤的特异性比99mTc-MDP骨显像高，在骨良恶性肿瘤鉴别诊断中具有重要的临床价值。