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 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.     

99mTc(V)-DMSA seintigraphy in monitoring the response of bone disease to vitamin D3 therapy in renal osteodystrophy

Renal osteodystrophy (ROD) is a common and serious complication for uremic patients and patients are treated with 1,25-dihydroxyvitamin D3. The bone scanning agent 99mTc-phosphate has also been used to evaluate in ROD but it is not clear that bone scintigraphy has a role in the follow-up of treatment. In this study 99mTc(V)-DMSA scintigraphy was performed in eleven patients [age 40.7 +/- 17.3 (mean +/- SD) yr] with ROD before and after vitamin D3 therapy. Images were obtained after hemodialysis performed following tracer injection to maintain normal blood levels of the radiopharmaceutical and to reduce soft tissue activity. Lumbar vertebra-to-soft tissue uptake ratios (LUR) were quantified with the planar 99mTc(V)-DMSA images. Alkaline phosphatase and parathyroid hormone levels after treatment had significantly decreased compared with pre-therapy. In all patients there was visually decreased uptake in bone structures after treatment. After treatment the mean LUR ratio was significantly lower than those of before treatment (3.59 +/- 2.63 vs. 1.65 +/- 0.62; p = 0.01). LUR values were correlated with pre-therapy alkaline phosphatase and parathyroid hormone. These findings indicate that 99mTc(V)-DMSA scintigraphy is sensitive in evaluating the response of ROD to vitamin D3 therapy.     

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: from freshly prepared reagents, through the use of a two component kit and 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.     

A micro-autoradiographical study of the localization of 99mTc(Sn)-MDP and 99mTc-MDP in undecalcified bone sections

The localization of ^99mTc(Sn)-MDP in bone tissue was compared with ^99mTc-MDP by means of microautoradiography of undecalcified bone sections. Sections of good histological quality were obtained by a rapid embedding method in methylmethacrylate. No differences were found in the localization of these radiopharmaceuticals in fetal rat calvariae after incubation in vitro or in rat femora after administration in vivo. In the incubation experiment, hydrolyzed ^99mTc was formed. The uptake was high in areas of new bone formation. No uptake was seen in cells or in resorbing areas. In compact bone ^99mTc(Sn)-MDP was predominantly taken up in the vicinity of blood vessels.     

Correlation between 99mTc-(V)-DMSA uptake and constitutive level of phosphorylated focal adhesion kinase in an in vitro model of cancer cell lines

Purpose Although a number of prognostic indicators have been developed, it is still difficult to predict the biological behaviour of all cancer types. ^99mTc-(V)-DMSA (V DMSA) uptake and focal adhesion kinase (FAK) expression and activation level could be potential agents for this purpose. We hypothesised the existence of a correlation between V DMSA, whose uptake is linked to phosphate ions, essential compounds for tumour growth and cell proliferation, and the adhesion protein FAK, whose elevated expression and level of constitutive activation are implicated in cancer progression. The aim of this study was to assess the relationship between V DMSA incorporation rate and FAK expression and activation by phosphorylation on tyrosine 397 residue.Methods We determined V DMSA uptake in six different cancer cell lines and we measured FAK expression and activation by using Western Blotting analysis. Correlations with factors known to be associated with poor prognosis, such as invasive potential, resistance to chemotherapy and proliferation rate, were also investigated. Results The cell lines exhibited different V DMSA incorporation rates. In addition, these cells showed the same FAK expression, but various degrees of activation. A correlation was observed between V DMSA uptake and level of FAK phosphorylation and between V DMSA or constitutive FAK activation and proliferation rate. However, no correlation was shown between these parameters and the other factors tested, i.e. invasive potential and anticancer drug resistance.Conclusion The results of this in vitro study clearly demonstrate that phosphorylation of FAK, proliferation rate and V DMSA uptake are closely related. Because proliferation and a high level of constitutive FAK activation are linked to cancer progression, it can be assumed that in vivo V DMSA uptake reflects tumour aggressiveness.     

99Tcm(V)-DMSA显像诊断急慢性骨关节炎价值的研究

目的 :研究99Tcm(V) DMSA(二巯基丁二酸钠 )SPECT显像对急慢性骨关节炎的诊断价值。方法 :急性化脓性骨关节炎患者 17例和慢性骨关节病患者 19例行99Tcm(V) DMSA显像 ,并进行半定量分析。结果 :99Tcm(V) DMSA在急性化脓性骨关节炎病灶处有明显趋骨性浓集 ;而慢性骨关节疾病病灶处99Tcm(V) DMSA显像也有明显的趋骨浓集。半定量分析示99Tcm(V) DMSA显像急性化脓性骨关节炎的放射性靶与非靶组织比值 (L/N)为 3.4 95± 0 .74 2 ,慢性骨关节病的放射性靶与非靶组织比值 (L/N)为 3.14 4± 0 .4 0 0 ,二者之间没有明显差异 (P >0 .0 5 )。结论 :99Tcm(V) DMSA可用于骨组织急慢性炎症的诊断 ,但不能区分骨组织病变的良恶性质。     

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.     

Esophageal dischalasia: Serendipity during 99mTc thyroid scan

It is rare for a large amount of pooled radioactive saliva to be observed in the neck during a thyroid scan. Such a finding would imply abnormal salivation and/or esophageal kinesis. The case of esophageal dischalasia reported here suggests that a complete study of the esophagus is advisable when a large area or amount of radioactive saliva is observed in the neck during a thyroid scan.     

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.     

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     

The Clinical Usefulness of 99mTc HMPAO Leukocyte/99mTc Phytate Bone Marrow Scintigraphy for Diagnosis of Prosthetic Knee Infection: A Preliminary Study

Purpose

The preferred radionuclide imaging procedure for diagnosing prosthetic joint infection is combined radiolabeled leukocyte/^99mTc sulfur colloid bone marrow scintigraphy, which has an accuracy of over 90 %. Unfortunately, sulfur colloid is no longer available in South Korea. In this study, we evaluated the usefulness of ^99mTc phytate, a substitute for ^99mTc sulfur colloid, when combined with radiolabeled leukocyte scintigraphy in suspected prosthetic knee infections.

Methods

Eleven patients (nine women, two men; mean age 72 ± 6 years) with painful knee prostheses and a suspicion of infection underwent both ^99mTc HMPAO leukocyte scintigraphy (LS) and ^99mTc phytate bone marrow scintigraphy (BMS). The combined images were interpreted as positive for infection when radioactivity in the LS at the site of clinical interest clearly exceeded that of the BMS (discordant); they were interpreted as negative when the increased activity in the LS was consistent with an increased activity in the BMS (concordant). The final diagnosis was made with microbiological or intraoperative findings and a clinical follow-up of at least 12 months.

Results

Five of eleven patients were diagnosed as having an infected prosthesis. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the combined LS/BMS were 100 %, 83 %, 83 %, 100 % and 91 %, respectively.

Conclusion

We find that combined ^99mTc HMPAO LS/^99mTc phytate BMS shows comparable diagnostic performance to other studies utilizing sulfur colloid. Combined ^99mTc HMPAO LS/^99mTc phytate BMS is therefore expected to be an acceptable alternative to combined radiolabeled LS/^99mTc sulfur colloid BMS for diagnosing prosthetic knee infections.     

Isolation and labelling of human leukocytes with 99mTc

The role of the leukocyte isolation procedure on cell labelling with ^99mTc has been evaluated. Separation of leukocytes was performed by two procedures: (1) sedimentation on methyl cellulose, followed by discontinuous gradient centrifugation; (2) methyl cellulose sedimentation and hypotonic haemolysis of residual red blood cells. After washing the cells in saline and incubation with a stannous pyrophosphate agent, the leukocytes were labelled with 5–10 mCi ^99mTc. Procedure 1 gave a higher purity but lower recovery of polymorphonuclear leukocytes, and a minor contamination of red blood cells. ^99mTc labelling of cells was slightly more efficient with this method, probably due to the presence of red blood cells. Procedure 1 is recommended for in vitro studies on cell kinetics and procedure 2 is recommended for clinical use.     

Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC) : a clinical evaluation

A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n=4) and patients (n=20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma halflife of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning.     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

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     

Use of pertechnetate 99mTc for abdominal scanning in localising an ileal duplication cyst: case report and review of the literature

A 10-year-old boy presented with periumbilical postprandial pain and some melena. Physical examination was normal. All investigations were negative except a pertechnetate ^99mTc abdominal scan which showed a very large and horn-shaped focus of high activity in the right flank. An ileal duplication was resected. It was lined by antral gastric mucosa with a large ulcer. The patient was treated successfully. The abdominal pertechnetate scan is discussed. Offprint requests to: X. Marchandise     

Diffuse pulmonary uptake of 99mTc bone-imaging agents: Case report and survey

Over the past 5 years, we have encountered 6 cases of diffuse pulmonary uptake of ^99m-Tc bone-scanning agents (incidence, 0.04%). To assess the significance of this phenomenon, we reviewed all of the cases reported since 1974 (Including our series, a total of 32 cases). Three groups can be discerned, the first consisting of 24 patients without radiological calcifications in the lungs and with hypercalcemia of different origins (mostly hyperparathyroidism). Of the eight autopsies performed in this group, seven revealed extensive calcifications in alveolar walls and lung vessels; the other autopsy showed no calcification at all and only bronchopneumonic lesions. The second group consists of 6 patients in chronic dialysis. The last group consists of 2 patients having diffuse pulmonary alveolar microlithiasis with extensive radiologic calcifications.The mechanism of lung uptake of ^99m-Tc bone-imaging agents is probably the same as that of bone uptake (chemisorption on hydroxyapatite crystals), although other uptake mechanisms have also been discussed.Bone scintigraphy can be useful in the detection of early pulmonary calcifications, which have been associated with impaired pulmonary function and, due to their size, are generally not detected by X-ray.     

Dramatic intestinal uptake of99mTc pertechnetate in a pediatric patient with enteritis

A pediatric patient with enteritis, which showed dramatically diffuse uptake of 99mTc pertechnetate in the intestine, is reported. Repeated study after medical treatment exhibited complete disappearance of the intestinal uptake. 99mTc pertechnetate scintigraphy has the potentiality for diagnosing and monitoring active enteritis.