The continuing development and evaluation of new radiopharmaceuticals with high organ specificity, high photon yield and low patient dose is of utmost importance in nuclear medicine. A major breakthrough has yet to be achieved in the continuing search for a 99mTc labeled renal function agent for replacing 131I-orthoiodohippurate which has suboptimal emission characteristics for use with the imaging equipment and imparts a relatively high radiation absorbed dose to kidneys and bladder particularly in patients with renal dysfunction. The currently proposed project envisages the design and synthesis of specific organic compounds which are analogs of hippuran and other agents with known or anticipated renal tubular secretion as well as glomerular filtration which would enable the formulation of new 99mTc labeled renal agents for use in the clinical evaluation of effective renal plasma flow. They contain the R-CO-NH-CH2-COOH grouping analogous to that in hippurate, and consequently may provide the substrate specificity for renal excretion of this group of agents labeled with 99mTc. Efforts will be directed towards the synthesis of new agents followed by purification and characterization of the compounds by chemical, chromatographic and spectroscopic techniques and elemental analysis. Radiolabeling with 99mTc followed by in vitro and in vivo stability and characterization of the complexes will be thoroughly explored. Detailed biodistribution of the preparations in small animals and renal extraction efficiency and renal transport clearance in particular will establish the suitability of the agent for the anticipated clinical application in comparison with the currently available renal agents. The effect of renal tubular inhibitors on the uptake and excretion of promising agents will be studied to determine the renal transport system involved. After establishing the toxicity of the most promising agents, they will be compared with the renal agents in vogue for determination of the effective renal plasma flow. The main objective to develop new 99mTc labeled agents for renal perfusion and tubular function studies for diagnosis of different renal diseases will be met within the scope of the current project with the desired characteristics of providing a high target to background ratio with a short effective half life and minimal radiation dose.
| Bhargava, K K; Zhang, Z Y; Palestro, C J et al. (1999) Synthesis of aminobenzyltriethylenetetraaminohexaacetic acid: conjugation of the chelator to protein by an alkylamine linkage. J Protein Chem 18:761-70 |
| Zhang, Z; Bhargava, K K; Chun, S B et al. (1989) Technetium-99m labeled p-aminohippuric acid analogues: renal function agents. J Pharm Sci 78:829-32 |
| Lan, J A; Chervu, L R; Johansen, K L et al. (1988) Uptake of technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes. Gastroenterology 95:1625-31 |
| Finkel, J; Chervu, L R; Bernstein, R G et al. (1988) Red blood cell labeling with technetium-99m. Effect of radiopaque contrast agents. Clin Nucl Med 13:166-8 |
| Bhargava, K K; Chervu, L R (1987) N-hydroxysuccinimide-hippuran ester: application for radiolabeling of macro-molecules. Biochem Biophys Res Commun 144:323-8 |
