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Quantitation of renal uptake of technetium-99m DMSA using SPECT.

Quantitative single photon emission computed tomography (SPECT) methodology based on calibration with kidney phantoms has been applied for the assessment of renal uptake of [99mTc]DMSA in 25 normals; 16 patients with a single normal kidney; 30 patients with unilateral nephropathy; and 17 patients with bilateral nephropathy. An excellent correlation (r = 0.99, s.e.e. = 152) was found between SPECT measured concentration and actual concentration in kidney phantoms. Kidney uptake at 6 hr after injection in normals was 20.0% +/- 4.6% for the left and 20.8% +/- 4.4% for the right. Patients with unilateral nephropathy had a statistically significant (p less than 0.001) low uptake in the diseased kidney (7.0% +/- 4.7%), but the contralateral kidney uptake did not differ from the normal group (20.0% +/- 7.0%). The method was especially useful in patients with bilateral nephropathy. Significantly (p less than 0.001) decreased uptake was found in both kidneys (5.1% +/- 3.4% for the left and 6.7% +/- 4.2% for the right). The total kidney uptake (right and left) in this group showed to be inversely correlated (r = 0.83) with serum creatinine. The uptake of [99mTc]DMSA in single normal kidney was higher (p less than 0.001) than in a normal kidney (34.7% +/- 11.9%), however, it was lower than the total absolute uptake (RT + LT = 41.5% +/- 8.8%) in the normal group. The results indicate that SPECT is a reliable and reproducible technique to quantitate absolute kidney uptake of [99mTc]DMSA.

Adolescent↗

Renal handling of technetium-99m DMSA: evidence for glomerular filtration and peritubular uptake.

The finding of an enhanced excretion of [99mTc]dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of [99mTc]DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of [99mTc]DMSA in a human volunteer was 5.8%. Continuous infusion of [99mTc]DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of [99mTc]DMSA 34 +/- 4 ml/min, urinary clearance of [99mTc]DMSA 12 +/- 3 ml/min. The calculated filtered load of [99mTc]DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of [99mTc]DMSA.

Animals↗

The biological fate of 14C-dimercaptosuccinic acid in monkeys and rabbits.

The biological fate of 14C-labeled dimercaptosuccinic acid (DMSA) in monkeys and rabbits was determined by measuring the 14C activity in their urine, feces, and expired air (14CO2). Monkeys absorbed less than 20% DMSA from three oral dose levels (0.082, 0.16, and 0.5 mmol/kg) of 14C-DMSA, and the rabbits absorbed 32% DMSA or less from an oral dose of 14C-DMSA (0.5 mmol/kg). Although the bioavailability of DMSA was limited in either species, DMSA was detected in the blood of both species within minutes after oral dosing. In either species, most of the radiolabel from the absorbed 14C-DMSA was detected in the urine within 12 hours. We also developed a sensitive assay for directly measuring levels of DMSA (as free thiols) in blood. Intact DMSA was not detected in the blood of the monkeys or the rabbits more than 200 minutes after oral or intravenous dosing at 0.5 mmol DMSA/kg body weight. However, 14C activity in blood and urine of the monkeys was measurable 72 hours after this dose. Differences between measured 14C concentrations and intact DMSA concentrations in the blood suggest the presence of DMSA metabolites that have longer half-lives than DMSA. Consequently, until the biological activities of these compounds are identified, the pharmacokinetic analysis of DMSA may be incomplete.

Animals↗

Tc-99m-(V)-DMSA: the new sensitive and specific radiopharmaceutical for imaging metastases of medullary thyroid carcinomas?

In the follow-up of five patients with histologic proven medullary thyroid carcinoma (MTC) and raised serum calcitonin and CEA levels the pentavalent Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan had the highest sensitivity in the localisation of metastases. Both methods are not tumor specific. A false positive Tc-99m-(V)-DMSA uptake in an old osteomyelitis of one vertebra could be demonstrated. The J-123-MIBG and In-111-F(ab2)' antibody scan did not allow to localise one of the above described metastases. In conclusion in the follow-up of patients with MTC and elevated tumor marker concentrations the Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan should be the second diagnostic procedures after sonography has been performed.

Adult↗

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.

Aged↗

99Tcm(v)-DMSA planar scintigraphy: does it have a role in the management of patients with head and neck squamous carcinoma?

99Tcm(v)-DMSA is a new tumour-imaging agent which has recently been proposed as a scintigraphic marker for head and neck squamous cell carcinoma (SCC). Seventy-seven patients were studied prospectively, of whom 58 had a history and diagnosis of head and neck SCC. All patients were examined, imaged using 99Tcm(v)-DMSA planar scintigraphy and then followed up clinically. In addition, 35 patients were followed up with scintigraphy (81 studies). Scintigraphy was less sensitive and less accurate than clinical examination for the overall detection of patients with SCC, for the detection of patients with SCC at presentation and for the detection of patients with primary tumours, possible nodal disease and with residual and recurrent disease following surgery and irradiation. Approximately 50% of patients exhibited positive uptake of 99Tcm(v)-DMSA in the salivary glands following radiotherapy. Although 99Tcm(v)-DMSA is accumulated at sites of head and neck SCC, its inability to detect low volume disease and apparent low specificity following surgery and irradiation means it has no role to play in the routine evaluation of patients with head and neck SCC.

Adult↗

Chelation of lead during co-exposure to ethanol.

Efficacy of calcium disodium EDTA, D-penicillamine (DPA), 2,3 dimercaptosuccinic acid (DMSA), and alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) to reduce the body burden of lead and restore the altered biochemical variables in lead or lead + ethanol administered rats was investigated. The investigation was aimed to suggest suitable prophylaxis of lead intoxication prevalent among workers co-exposed to lead and alcohol ingestion. Administration of lead (10 mg/kg, oral, once daily for 8 weeks) produced a significant inhibition in the activity of blood delta-aminolevulinic acid dehydratase (ALAD), elevation in the blood zinc protoporphyrin (ZPP) and urinary elimination of lead and delta-aminolevulinic acid (ALA). Lead contents of blood, liver, kidney and brain were also significantly higher than the normal control. The above changes were more marked in animals co-exposed to lead + ethanol (20% in drinking water) compared to lead alone. All the chelators were effective in increasing the urinary lead elimination, reducing the above biochemical alterations and lead contents of tissues. The order of effectiveness being DMSA greater than Calcium disodium EDTA greater than DPA greater than MFA. However, the protection was more noticeable in animals treated with lead alone than with lead and ethanol.

Acrylates↗

[Renal artery thrombosis in newborn infants undergoing umbilical artery catheterization].

A prospective study to detect renal artery thrombosis by radionuclide renal scintigraphy in newborn infants who underwent umbilical arterial catheterization over a one year period was done: 62 babies were catheterized, 92% were preterm and 85% had severe respiratory distress syndrome that required mechanical ventilation, 25/62 (40.3%) survived and in all of them Tc-99m DMSA scans were taken at a median of 5 days after withdrawal of the umbilical artery catheters (range 9 h to 29 days). A baby with renovascular hypertension had a DMSA scan which showed segmental vascular defect in one kidney. Another patient had left iliac artery thrombosis and two others showed evidence of transient vasospasm. Death occurred in 37/62 (59.7%), 92% of whom underwent autopsy studies which showed aortoiliac thrombosis in 8.8%, all of them without clinical symptoms. Other 12 newborn infants who died without previous umbilical artery catheterization had no evidence of thrombosis at autopsy.

Catheterization↗

Experience in imaging medullary thyroid carcinoma using 99mTc (V) dimercaptosuccinic acid (DMSA).

99mTc (V) dimercaptosuccinic acid (DMSA) is a new tumor imaging agent that has been successfully used to image patients with medullary thyroid carcinoma (MTC). Since 1986, studies have been performed in 32 patients with histologically proven MTC at Guy's Hospital, London, England. Five patients with primary tumor were studied prior to surgery, four patients were studied after successful removal of the primary tumor, and 26 patients with biochemical evidence of recurrence were studied. Eight patients were studied serially to assess progression of disease, and four patients were studied before and after surgery. Twenty-one of the 26 patients with disease had positive scans with four false-negative scans and three true negative scans. One patient had a false-positive scan (sensitivity 80%, specificity 75%). Two of the false-negative scans were obtained in patients with moderate but stable elevations of calcitonin but no other evidence of recurrence. One false-negative scan was obtained in a patient who was discovered on screening to have an abnormal pentagastrin response, and a small 1 cm tumor was subsequently removed. Uptake in local neck recurrence was frequently intense, but uptake at sites of bone metastases was less marked. 99mTc (V) DMSA is an inexpensive radiopharmaceutical which produces good quality images and has been shown to have an acceptable sensitivity and specificity in the follow-up of patients with MTC and thereby contributes significantly to the management of these patients.

Adolescent↗

The role of radiopharmaceuticals MIBG and (V) DMSA in the diagnosis of medullary thyroid carcinoma.

The diagnostic value of 123/131I meta-iodo-benzylguanidine (MIBG) and 99mTc (V) dimercaptosuccinic acid (DMSA) was investigated in 12 patients with proven medullary thyroid carcinoma (MTC). Scintigraphic imaging with DMSA was negative in nine of 12 patients. Scintigraphy with MIBG was positive in only one case. In proven primary or recurrent disease, DMSA sensitivity was 50% and MIBG sensitivity was 25%. Such sensitivities become much lower in subjects with high calcitonin (CT) levels who have had negative surgical explorations: DMSA 17% and MIBG 0%. DMSA detected tumor in 25% of the patients and MIBG in only 8%. The positivity of these scintigraphies appears to be unrelated to carcinoembryonic antigen and CT plasma levels. Such data suggest that scintigraphies with MIBG and DMSA are only modestly useful in the diagnosis of MTC.

3-Iodobenzylguanidine↗

Diagnostic and therapeutic potential of new radiopharmaceutical agents in medullary thyroid carcinoma.

Recently developed radiopharmaceuticals have been proposed for imaging medullary thyroid carcinoma (MTC) with some having therapeutic potential. This study compares the imaging results obtained with radioiodinated meta-iodo-benzylguanidine (MIBG), 99mTc (V) DMSA, and 131I F(ab')2 anti-carcinoembryonic antigen (anti-CEA) in a group of MTC patients. In 23 patients 131I MIBG imaging showed a high specificity (no false-positive results) but a less satisfactory sensitivity (50%). In 12 patients 99mTc (V) DMSA revealed a better sensitivity (77%) but a lower specificity (three false-positive results). Positive results were obtained in two of three patients studied with 131I F(ab')2 anti-CEA. These data suggest that the highly sensitive 99mTc (V) DMSA should be considered as a first choice procedure followed by the highly specific radioiodinated MIBG to confirm the initial results. Since radioiodinated MIBG imaging may have therapeutic usefulness, 131I MIBG was evaluated in an integrated treatment protocol in four cases of proven MTC. The preliminary results obtained were encouraging.

3-Iodobenzylguanidine↗

[Scintigraphic localization of the liver and kidneys for abdominal radiotherapy: methods, accuracy and comparison with the ultrasonic procedure].

The exposure of liver and kidney has to be avoided when irradiation fields for radiotherapy of the abdomen are planned and adjusted, unless these organs themselves are the target of therapeutic procedure. A scintigraphic method is presented which allows to transfer the site and borderlines of the organs to the body surface taking exactly into account the irradiation position. A precise transfer of site, size, and shape of the organs facilitates the adjustment of irradiation fields or the positioning of satellite field stops. Scintigraphic organ localization is performed by means of static liver or kidney scintigraphy with suitable radiocolloids for the liver and 99mTc DMSA for the kidneys. The scintigraphic procedure meets all practical requirements regarding the precision of organ localization and shows evident advantages compared to X-ray and ultrasonographic methods. It can be performed at every department of nuclear medicine without preparing the patient and is not influenced by intestinal air artefacts, skeletal parts, obesity, or dystopic organ sites. The results of scintigraphic and ultrasonographic kidney localisation are compared in 15 patients. The scintigraphic procedure has shown to be superior, even with regard to precision and possibility of variable projections to the body surface.

Abdominal Neoplasms↗

Combination of DMSA-scintigraphy and hippuran renography in unilateral obstructive nephropathy. Improved prediction of recovery after intervention.

The renal handling of dimercaptosuccinic acid and hippuran differs. This might be used in unilateral obstructive nephropathy in order to predict potential functional recovery following intervention. The theory was evaluated on a retrospective basis in 17 patients, who primarily had a nephrostomy. If the DMSA-uptake rate in the diseased kidney was more than 10 per cent higher than that of hippuran, the uptake rate of hippuran increased following relief of obstruction. Use of the two radiopharmaceuticals, thus, may have great impact on the clinical decision, since in case of a difference some function may be saved by immediate intervention.

Female↗