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.     

Technetium-99m sestamibi: an indicator of breast cancer invasiveness

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with ^99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revision showed a positive ^99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm² and one showed 99 microvessels/mm²; by contrast there were 71.6±12.1 microvessels/mm² in the nine N- and sestamibi-negative tumours. Our study suggests that ^99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour.     

Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer

Quantitative ^99mTc-dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute ^99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between ^99mTc-DMSA uptake and cumulative ifosfamide dose was found (P<0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. ^99mTc-DMSA uptake was more consistent than ₂-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. ^99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced ^99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that ^99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.     

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     

Technetium-99m benzimidazolyl iminodiacetic acid hepatobiliary radiopharmaceuticals: structure biodistribution studies

The biodistribution of fifteen structural variants of the hepatobiliary radiopharmaceutical, technetium-99m benzimidazolyl iminodiacetic acid (BIMIDA) were determined 1 h after i.v. injection into rats. The best compounds with respect to hepatobiliary excretion were those with halogen substituents in the benzene ring of the BIMIDA ligand. The cholescintigraphic properties of the BIMIDA compounds compared favourably with those of technetium-99m acetanilido iminodiacetic acid (HIDA) radiopharmaceuticals.     

Myocardial infarct imaging in patients with technetium-99m 2,3-dimercaptosuccinic acid. Superiority of technetium-99m pyrophosphate

Technetium-99m 2,3-dimercaptosuccinic acid (Tc-99m DMSA) has been used successfully for imaging acute myocardial infarction in a canine model. The application in humans, however, has not been previously reported. In order to determine the feasibility of using this agent in clinical studies and to compare the agent to technetium-99m pyrophosphate (Tc-99m PPi), ten patients with proven myocardial infarction were studied. While imaging of transmural infarctions in humans was achieved using Tc-99m DMSA, scores for the Tc-99m DMSA images (1.8 +/- 0.96) were not as high as for Tc-99m PPi (2.5 +/- 0.45) (P less than 0.05). Discordance among four independent interpreters was greater for images obtained with Tc-99m DMSA. The superiority of Tc-99m PPi was evident whether images were obtained early (within 24 hours) or late (within five days). Although DMSA images were not obscured by rib uptake, they were less sensitive (63%) than Tc-99m PPi (97%). A potential advantage of Tc-99m DMSA in imaging acute myocardial infarction is that radiotracer concentration in the infarct occurs primarily in the early postinfarction period. The longer postinfarction that Tc-99m DMSA imaging was attempted, the lower the concentration of radiotracer. Thus, Tc-99m DMSA would not be expected to have the same persistence pattern as Tc-99m PPi into the remote postinfarction period. The persistent positivity of Tc-99m PPi has made it difficult to diagnose reinfarction.     

Technetium-99m HYNIC-annexin V: a potential radiopharmaceutical for the in-vivo detection of apoptosis

Either inadequate or excessive apoptosis (programmed cell death) is associated with many diseases. A method to image apoptosis in vivo, rather than requiring histologic evaluation of tissue, could assist with therapeutic decision making in these disorders. Programmed cell death is associated with a well-choreographed series of events resulting in the cessation of normal cell function, and the ultimate disappearance of the cell. One component of apoptosis is signaling adjacent cells that this cell is committing suicide by externalizing phosphatidylserine to the outer leaflet of the cell membrane. Annexin V, a 32-kDa endogenous human protein, has a high affinity for membrane-bound phosphatidylserine. We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo. In this report we describe the results of a series of experiments in mice and rats to characterize the biologic behavior of ^99mTc-HYNIC- annexin V. Biodistribution studies were performed in groups of rats at 10–180 min after intravenous injection of ^99mTc-HYNIC-annexin V. In order to estimate the degree of apoptosis required for localization of ^99mTc-annexin V in vivo, mice were treated with dexamethasone at doses ranging from 1 to 20 mg/kg, 5 h prior to ^99mTc-HYNIC-annexin V administration, to induce thymic apoptosis. Thymus was excised 1 h after radiolabeled HYNIC-annexin V injection; thymocytes were isolated, incubated with Hoechst 33342 followed by propidium iodide, and analyzed on a fluorescence-activated cell sorter. Each sorted cell population was counted in a scintillation counter. To test ^99mTc-HYNIC-annexin V as a tracer for external radionuclide imaging of apoptotic cell death, radionuclide imaging of Fas-defective mice (lpr/lpr mice) and wild-type mice treated with the antibody to Fas (anti-Fas) was carried out 1 h post injection. Rat biodistribution studies demonstrated a blood clearance half-time of less than 10 min for ^99mTc-HYNIC-annexin V. The kidneys had the highest concentration of radioactivity at all time points. Studies in the mouse thymus demonstrated a 40-fold increase in ^99mTc-HYNIC-annexin V concentration in apoptotic thymocytes compared with the viable cell population. A correlation of r=0.78 was found between radioactivity and flow cytometric and histologic evidence of apoptosis. Imaging studies in the lpr/lpr and wild-type mice showed a substantial increase of activity in the liver of wild-type mice treated with anti-Fas, while there was no significant change, irrespective of anti-Fas administration, in lpr/lpr mice. Excellent images of hepatic apoptosis were obtained in wild-type mice 30 min after injection of ^99mTc-HYNIC-annexin V. The imaging results were consistent with histologic analysis in these animals. In conlusion, these studies confirm the value of ^99mTc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo. Received 22 February and in revised from 5 May 1999     

Technetium-99m complex ofN-(2-pyridylmethyl)iminodiacetic acid as a new renal radiopharmaceutical

A tetradentate chelating agent constituting of an iminodiacetic acid group and a nitrogen atom of pyridine, N-(2-pyridylmethyl)iminodiacetic acid (PMIDA), was coordinated with 99mTc and evaluated as a renal functional agent. The complex of PMIDA with 99mTc was prepared by using a stannous chloride solution as a reducing agent. The chelating efficiency was analyzed by thin layer chromatography and electrophoresis. Chelation with 99mTc resulted in a single radiochemical product. Biological studies were performed in mice and rats. 99mTc-PMIDA was removed from the circulation solely by the kidneys. Clearance of 99mTc-PMIDA from the blood and the kidneys was as rapid as that of 99mTc-diethylenetriaminepentaacetic acid. The rate of blood clearance was unaffected by the administration of probenecid (a test for tubular secretion by the weak-acid mechanism), so that the glomerular filtration rate could be estimated by measuring its clearance from the blood. The results in animals with myohemoglobinuric acute renal failure suggested that 99mTc-PMIDA might be a useful renal function radiopharmaceutical.     

Technetium-99m (99mTc) mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent.

Technetium-99m (99mTc) mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical that was recently introduced as a 99mTc-labeled replacement for iodine-131 (131I) o-iodohippurate (OIH). Since its introduction, a wide variety of in vitro and in vivo studies have been performed to characterize the high-performance liquid chromatography (HPLC)-purified complex and kit formulations. [99mTc]MAG3 has a slower plasma clearance, a higher plasma protein binding, less red blood cell (RBC) penetration, a lower extraction ratio, and a smaller volume of distribution than OIH. Because of the slower plasma clearance, [99mTc] MAG3 cannot be used as a direct measurement of effective renal plasma flow. Simplified methods have been developed to calculate [99mTc]MAG3 clearances, as well as regression equations to convert these clearances to an equivalent OIH value. The image quality of [99mTc]MAG3 is superior to [131I]OIH; the renogram curves and the fraction of the dose of the two agents that appears in the urine are almost identical, even though the plasma clearance of [99mTc]MAG3 is only 50% to 65% that of OIH. [99mTc]MAG3 compares favorably with OIH in patients with a wide range of clinical problems. The radiation dose to a patient with normal renal function using standard imaging doses is higher for [99mTc]MAG3 than for [131I]OIH, but in patients with impaired renal function, the radiation dose from [131I]OIH is much higher than [99mTc]MAG3. [99mTc]MAG3 also provides superior image quality compared with [99mTc]diethylenetriaminepentaacetic acid (DTPA) in patients with impaired renal function, but it is important to note that [99mTc]MAG3 cannot be used to measure the glomerular filtration rate (GFR). [99mTc]MAG3 is the most promising 99mTc tubular function agent to date, and it has replaced OIH and [99mTc]DPTA in a number of institutions. However, there are physiologic differences between these three agents and, therefore, they should not be expected to behave identically in all clinical conditions.     

Usefulness of (99m)Tc(V)-dimercaptosuccinic acid scintigraphy in the assessment of response to external radiation therapy in soft tissue sarcoma in Giant Snauzer dog

A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic evaluation with a history of malignant fibrosarcoma with a rapidly growing non painful mass on the left shoulder region quite near to the site of an operation performed four months ago. We carried out oncological scintigraphy using pentavalent (99m)Technetium labelled dimercaptosuccinic acid [(99m)Tc(V)-DMSA], a tumour localising radiopharmaceutical agent. The study was performed to assess the margins, vascularity of the tumour and response to the cancer therapy. Uniform intense radiopharmaceutical uptake was observed in the lesion indicating its margins, vascularity and malignant nature. The dog was subjected to external radiation therapy to control the growth of the cancer and to bring the tumour mass to an operable size. The dog was followed up with (99m)Tc(V)-DMSA scintigraphy pre-irradiation and post-irradiation. Immediately after the post-irradiation scintigraphy, the dog was operated on. During the surgery, resection of the tumour margins was performed carefully using a hand held gamma probe to assure that no tumour tissue was left inside. In conclusion, the authors would like to state that (99m)Tc(V)-DMSA oncoscintigraphy is valuable in the assessment and evaluation of therapy in canine soft tissue cancer.     

Technetium-99m HYNIC-annexin V: a potential radiopharmaceutical for the in-vivo detection of apoptosis.

Either inadequate or excessive apoptosis (programmed cell death) is associated with many diseases. A method to image apoptosis in vivo, rather than requiring histologic evaluation of tissue, could assist with therapeutic decision making in these disorders. Programmed cell death is associated with a well-choreographed series of events resulting in the cessation of normal cell function, and the ultimate disappearance of the cell. One component of apoptosis is signaling adjacent cells that this cell is committing suicide by externalizing phosphatidylserine to the outer leaflet of the cell membrane. Annexin V, a 32-kDa endogenous human protein, has a high affinity for membrane-bound phosphatidylserine. We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo. In this report we describe the results of a series of experiments in mice and rats to characterize the biologic behavior of (99m)Tc-HYNIC- annexin V. Biodistribution studies were performed in groups of rats at 10-180 min after intravenous injection of (99m)Tc-HYNIC-annexin V. In order to estimate the degree of apoptosis required for localization of (99m)Tc-annexin V in vivo, mice were treated with dexamethasone at doses ranging from 1 to 20 mg/kg, 5 h prior to (99m)Tc-HYNIC-annexin V administration, to induce thymic apoptosis. Thymus was excised 1 h after radiolabeled HYNIC-annexin V injection; thymocytes were isolated, incubated with Hoechst 33342 followed by propidium iodide, and analyzed on a fluorescence-activated cell sorter. Each sorted cell population was counted in a scintillation counter. To test (99m)Tc-HYNIC-annexin V as a tracer for external radionuclide imaging of apoptotic cell death, radionuclide imaging of Fas-defective mice (lpr/lpr mice) and wild-type mice treated with the antibody to Fas (anti-Fas) was carried out 1 h post injection. Rat biodistribution studies demonstrated a blood clearance half-time of less than 10 min for (99m)Tc-HYNIC-annexin V. The kidneys had the highest concentration of radioactivity at all time points. Studies in the mouse thymus demonstrated a 40-fold increase in (99m)Tc-HYNIC-annexin V concentration in apoptotic thymocytes compared with the viable cell population. A correlation of r=0.78 was found between radioactivity and flow cytometric and histologic evidence of apoptosis. Imaging studies in the lpr/lpr and wild-type mice showed a substantial increase of activity in the liver of wild-type mice treated with anti-Fas, while there was no significant change, irrespective of anti-Fas administration, in lpr/lpr mice. Excellent images of hepatic apoptosis were obtained in wild-type mice 30 min after injection of (99m)Tc-HYNIC-annexin V. The imaging results were consistent with histologic analysis in these animals. In conlusion, these studies confirm the value of (99m)Tc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo.     

Active inflammatory bowel disease: head-to-head comparison between 99mTc-hexamethylpropylene amine oxime white blood cells and 99mTc(V)-dimercaptosuccinic acid scintigraphy

PURPOSE: Evaluation and comparison between pentavalent 99mTc dimercaptosuccinic acid (99mTc(V)-DMSA) and 99mTc-hexamethylpropylene amine oxime white blood cell (99mTc-HMPAO WBC) scintigraphy in the detection and assessment of disease activity in patients with active inflammatory bowel disease (IBD). MATERIALS AND METHODS: 99mTc(V)-DMSA scintigraphy was performed in 23 patients with active IBD and true positive 99mTc-HMPAO WBC scintigraphy. Images were considered positive when an area of increased uptake was observed. To assess severity of IBD, semi-quantitative analysis was included with reference to the uptake in the iliac crest. Comparison with endoscopic, radiological and clinical data was performed. RESULTS: The diagnostic accuracy of 99mTc-HMPAO WBC and 99mTc(V)-DMSA was 91% and 84%, respectively. A significant correlation between the findings of both radioisotopic methods and scintigraphy score was demonstrated. Endoscopic findings were significantly correlated with scintigraphic results. Kappa statistics showed a moderate to good agreement between the two scintigraphic methods. Two patients (8.8%) had negative findings with 99mTc(V)-DMSA scintigraphy (false negative results). CONCLUSION: 99mTc(V)-DMSA compared to 99mTc-HMPAO WBC could provide a simple, non-invasive alternative method for the assessment of disease activity, although it is slightly inferior to 99mTc-HMPAO WBC scintigraphy especially in the evaluation of disease localization in IBD patients.     

Visualization of orbital retinoblastoma with technetium-99m (V) dimercaptosuccinic acid

The potential contributions of technetium-99m (V) dimercaptosuccinic acid scintigraphy in the evaluation of orbital retinoblastoma, its local extensions and metastases were assessed in this study. Both planar and SPECT images clearly demonstrated the primary tumor and metastatic sites. Following confirmation of our results by contemporaneous ultrasonography, MRI and a subsequent incisional biopsy, the patient was treated with external beam radiotherapy and chemotherapy. This preliminary study showed that in combination with other diagnostic tests, Tc-99m (V) DMSA scintigraphy may play a role in the detection and follow-up of the local tumor extensions and metastases in patients with retinoblastoma.