Synthesis and preclinical evaluation of technetium-99m-labeled hippurate analogues.
We have synthesized seven 99mTc-labeled hippurate analogues: 99mTc-hippurate. 99mTc-alpha-hydroxyhippurate, 99mTc-m-hydroxyhippurate. 99mTc-o-hydroxyhippurate [99m-salicylglycine (99mTc-SG)], 99mTc-p-hydroxyhippurate, 99mTc-salicylglycylglycine and 99mTc-salicylglycylglycylglycine. All of the 99mTc-hippurates were cleared rapidly from the rat blood and accumulated in the kidney. Of them 99mTc-SG has the desirable biological properties of two diagnostic agents. 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and 99mTc-dimercaptosuccinate (99mTc-DMSA). A fraction of 99mTc-SG showed a transit time in the kidney and was excreted rapidly into the urine, being similar to 99mTc-MAG3. The binding ratio to the plasma proteins was 96.0% (91.1% in the albumin), being higher than that of 99mTc-DMSA, at 30 min. The lipophilicity revealed far less pH-dependent changes in a range of pH 4.0 to 7.4. 99mTc-SG distributed about 91% in the renal cortex, being similar to that of 99mTc-DMSA. From the present studies, the biological properties of 99mTc-SG suggest that it is a promising agent for measuring renal plasma flow and renal morphology.
Fukuoka
M
M
Division of Biological Chemistry, National Institutes of Hygienic Sciences, Tokyo, Japan.
Kiyohara
T
T
Kobayashi
T
T
Kojima
S
S
Tanaka
A
A
Kubodera
A
A
D000818:Animals; D006626:Hippurates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D004113:Succimer / Q000493:pharmacokinetics; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D014018:Tissue Distribution
D006626:Hippurates; D015609:Organotechnetium Compounds; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D004113:Succimer