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Hypertension in children. Increased efficacy of technetium Tc 99m succimer in screening for renal disease.

Renal scintigraphy with technetium Tc 99m succimer (DMSA) and technetium Tc 99m pentetate (DTPA) was used to study 80 hypertensive pediatric and adolescent patients. Renal abnormalities such as asymmetry of function, size, or shape were identified in 13 patients. Both excretory urography and technetium Tc 99m pentetate studies were successful in detecting 54% of the abnormalities in patients studied; technetium Tc 99m succimer identified 92%. The accuracy of the latter was 96%, with a specificity of 97%. The ability of technetium Tc 99m succimer renal scintigraphy to identify accurately the presence or absence of renal abnormalities warrants its inclusion in the initial examination of pediatric and adolescent patients with hypertension.

Adolescent↗

Radionuclide imaging of myocardial perfusion and viability in assessment of acute myocardial infarction.

Technical advances in radionuclide imaging have important implications for the management of patients with acute myocardial infarction. Single-photon emission computerized tomography with thallium 201 (TI-201) offers greater accuracy than planar imaging in detecting, localizing and sizing myocardial perfusion defects. Use of single-photon emission computerized tomography with TI-201 should allow for a more accurate assessment of prognosis after myocardial infarction. A new radiopharmaceutical, technetium 99-m methoxyisobutyl isonitrile, provides a number of advantages over TI-201, including higher quality images, lack of redistribution, and the ability to assess first-pass ventricular function. Applications of TI-201 and technetium 99-m methoxyisobutyl isonitrile include assessment of arterial patency and myocardial salvage immediately after thrombolytic therapy, detection of resting ischemia after thrombolytic therapy, targeting of subsets of patients for further intervention, and predischarge assessment to predict the future course of patients after an acute myocardial infarction.

Coronary Circulation↗

Molecular weights of technetium hydroxyethylidene diphosphonate complexes.

The results of recycle size-exclusion and anion-exchange chromatography are combined to determine molecular weights and radii of gyration for selected components of a carrier-added technetium hydroxyethylidene diphosphonate radiopharmaceutical bone-imaging preparation. Samples evaluated by size-exclusion are selected from fractions collected as the preparation elutes from the anion-exchange column. Polyethylene glycol and polyphosphate molecular weight standards are used, in conjunction with the universal calibration method, to determine Mark-Houwink constants and to estimate molecular weights for the complexes. The results of this study support a spherical shape model for the collection of technetium complexes. Given the combined knowledge of molecular weights, charges, technetium concentration dependencies, and mass spectral data, several formula assignments are proposed, including TcO(OH)L-1, Tc2O(OH)6L-3, Tc2O(OH)2L3(-6), Tc3O2(OH)3L2(-5), Tc3O2(OH)3L3(-7), Tc2O2(OH)4(HL)3(-7) and Tc2O2(OH)4(H2L)4(-8).

Chemical Phenomena↗

Pentavalent [99mTc]DMSA, [131I]MIBG, and [99mTc]MDP--an evaluation of three imaging techniques in patients with medullary carcinoma of the thyroid.

Nine patients with histologically proven medullary carcinoma of the thyroid (MCT) were imaged using pentavalent [99mTc]dimercaptosuccinic acid [(V)DMSA], [131I] metaiodobenzylguanidine (MIBG) and [99mTc]methylene diphosphonate (MDP). Technetium-99m (V)DMSA demonstrated most of the tumor sites in eight patients with proven metastases, with an overall sensitivity of 95% in lesion detection. Iodine-131 MIBG showed definite uptake in some of the tumor sites in three of the nine patients imaged, with equivocal uptake seen in a further one patient, with sensitivity of only 11% for lesion detection. Technetium-99m MDP demonstrated bony metastases only, in four of the patients imaged yielding a sensitivity of 61%. Technetium-99m (V)DMSA has been demonstrated in this study to be a useful imaging agent in patients with MCT, showing uptake in significantly more lesions and with better imaging qualities than [131I]MIBG, and with the ability to detect soft tissue as well as bony metastases.

3-Iodobenzylguanidine↗

Potential pitfall of DMSA scintigraphy in patients with ureteral duplication.

A 5-wk-old male presented with radiographic findings of a duplicated collecting system. A [99mTc]DMSA scan was requested to evaluate cortical function. Images obtained immediately. postinjection showed activity restricted to the upper poles; in contrast, delayed images at 4 hr showed activity in the bladder and throughout both kidneys. Catheterizing the patient drained the activity from the bladder but had little effect on the refluxed renal activity. The early [99mTc]DMSA images were critical in making the proper interpretation. Technetium-99m DMSA is excreted into the urine and this fact needs to be considered when interpreting scans of patients with possible reflux or obstruction. When DMSA scans are obtained in pediatric patients with possible reflux, catheterization prior to the study and early images prior to the appearance of DMSA in the collecting system are recommended.

Humans↗

Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues.

Potent antagonists of bombesin-like peptides have shown great potential for applications in cancer therapy. A 99mTc-labeled agent capable of identifying patients who could benefit from these emerging therapies would have a great impact on patient management. This study involves the synthesis and initial evaluation of technetium diaminedithiolate analogues derived from the potent bombesin analogue Pyr-Gln-Lys-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 (Lys3-bombesin). We coupled two diaminedithiol (DADT) bifunctional chelating agents (BCAs 1 and 2) to the Lys3 residue at the N-terminal region that is not required for binding to the receptor. 99mTc labeling was performed by ligand exchange on addition of [99mTc]glucoheptonate to a solution of the adduct at room temperature. Two products were obtained from each adduct on analysis by HPLC. The major to minor product ratios of the 99mTc-labeled analogues were 3:1 for products from BCA 1 and 9:1 for the products from BCA 2. Macroscopic amounts of the 99Tc analogues were similarly prepared using [99Tc]glucoheptonate. In this case, the major to minor ratios were 2:1 for the products from both BCAs. For initial evaluation of the binding of the Tc-labeled peptides to bombesin receptors, the 99Tc analogues were used in vitro in competitive binding assays in rat brain cortex membranes against [125I-Tyr4]bombesin. Results of the in vitro assays showed that the inhibition constants (Ki) of the major and minor products were 3.5+/-0.7 and 3.9+/-1.5 nM, respectively, for the products from BCA 1; and 7.4+/-2.0 and 5.2+/-1.5 nM for the products derived from BCA 2, respectively. The high affinity exhibited by these technetium analogues is an indication of their potential for use in non-invasive in vivo biochemical characterization of cancers that possess receptors for bombesin.

Amino Acid Sequence↗

Pentavalent technetium-99m (V)-DMSA uptake in a pheochromocytoma in a patient with Sipple's syndrome.

This case report describes 99mTc(V)-dimercaptosuccinic acid (DMSA) accumulation in a pheochromocytoma in a patient with Sipple's syndrome. Scintigraphy with 99mTc(V)-DMSA demonstrated uptake in medullary carcinoma of the thyroid gland (MCT). Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy showed the bilateral pheochromocytomas but did not demonstrate uptake in the MCT.

3-Iodobenzylguanidine↗

Renal scintigraphy with technetium Tc 99m succimer: clinical utility in newborns with cystic renal dysplasia.

We have presented the case of a neonate with bilateral cystic renal dysplasia and normal pulmonary development, in whom technetium Tc 99m succimer scintigraphy demonstrated absence of normal renal cortical tubular tissue and correctly predicted that life-sustaining renal function would not occur. Since renal uptake of this radioactive agent depends on the functional mass of cortical tubular tissue, and the cystic dysplasias are characterized by abnormal dysplastic renal ductal and tubular tissue, this imaging agent can provide important prognostic information concerning renal function in these patients.

Humans↗

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.

Adult↗

Technetium-labelled autologous lymphocytes: clinical protocol for radiolabelling using a high concentration and low volume of 99Tcm-exametazime.

Little clinical work has been performed using technetium-labelled lymphocytes due to the difficulty of effecting an imaging dose of technetium on the small number of lymphocytes available. We have successfully labelled lymphocytes using a high concentration and low volume of 99Tcm-exametazime. In eight readings from three patients and two volunteers, the labelling efficiency was 27% (4 S.D.). The radiolabel was stable in plasma in vitro up to 4 h. Viability of the lymphocytes as determined by trypan blue exclusion was greater than 95%.

Blood Specimen Collection↗

Time dependence of iprofenin-labeling with technetium Tc 99m.

The incubation time required to attain 90% labeling efficiency (90% radiochemical purity) for technetium Tc 99m labeling of iprofenin (PIPIDA, Diagnostic Isotopes, Inc.), was investigated. Thirty iprofenin vials were prepared according to the manufacturer's instructions. Aliquots were withdrawn from 12 vials at times 0.5, 1, 2, 3, 5, 7, 10, 12, 15, 20, 30, 45, and 60 minutes after mixing. Aliquots were withdrawn from 18 vials at 1, 2, 3, 5, 7, and 10 minutes. Free pertechnetate and reduced/hydrolyzed technetium were isolated from aliquots with instant thin-layer chromatography and quantified with a scintillation well counter. Based on the 30 vials, a mean (+/- S.E.M.) of 5.83 +/- 4.32 minutes was required to attain 90% labeling efficiency. Using tolerance limits calculations, the incubation time required to be assured that 95% of vials have achieved 90% labeling is 16.8 minutes. It is concluded that 99mTc iprofenin vials should be incubated 17 minutes to be assured of 90% labeling efficiency.

Imino Acids↗

Uterine technetium-99m mercaptoacetyltriglycine and diethylene triamine penta-acetic acid uptake in the scintigraphic evaluation of transplanted kidneys.

An anuric 35-year-old woman with a renal transplant underwent serial renal scintigraphy studies to screen the kidney function. A hypervascular pelvic mass in the region of the bladder was identified during technetium-99m mercaptoacetyltriglycine (MAG3) and also during 99mTc diethylene triamine penta-acetic acid (DT-PA) scintigraphy. She was in the secretory phase of the uterine cycle during the study and had no gynaecological problem to explain the radioactivity accumulation. The accumulation of 99mTc-MAG3 mimicking the bladder was considered as uterine activity. To our knowledge, this is the first case of uterine visualization with 99mTc-MAG3.

Adult↗

Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.

Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.

Animals↗

Imaging of experimental myocardial infarction with technetium-99m 2,3-dimercaptosuccinic acid.

We have studied the use of Tc-99m-labeled 2,3-dimercaptosuccinic acid (Tc-99m DMSA) to scintigraph acute myocardial infarction after coronary occlusion in dogs. Optimal images were obtained 5 hr after injection of radiotracer, with consistent delineation 48 hr after occlusion. Delivery of tracer was dependent on blood flow. Uptake of tracer correlated to extent of infarction as determined by the myocardial depletion of creatine kinase. Myocardial Tc-99m DMSA was protein-bound.

Animals↗

Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease.

Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery diseaes. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 +/- 34.7 vs 33 +/- 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p less than 0.0001). Estimated defect size in the stress Tl-201 images (52 +/- 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 +/- 39.9 g; p less than 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT.

Coronary Disease↗

Technetium-99m DMSA imaging and the obstructed kidney.

Although several authors have claimed that the function of an obstructed kidney could be overestimated on Tc-99m DMSA imaging, the clinical importance of such an overestimation has not been well documented. Partial obstruction of one ureter was created in a rat, and a relative Tc-99m DMSA uptake was obtained 4 hours after intravenous injection. By puncture of the isolated obstructed kidney, it was shown that the function of that kidney was overestimated by at least 17%.

Animals↗