Technetium-99m DADS complexes as renal function and imaging agents: II. Biological comparison with iodine-131 hippuran.
To find a 99mTc agent with a high renal extraction efficiency similar to [131]hippuran, 21 analogs of DADS were labeled and evaluated. Preliminary screening by serial gamma camera imaging in rabbits showed that most analogs had a higher liver uptake and/or slower renal clearance, than hippuran. Three agents (P-DADS, AP-DADS, and CAP-DADS), exhibiting a relatively rapid blood clearance and lower liver uptake in the rabbit, were studied in greater detail in comparison with hippuran and CO2-DADS-A, the best analog to date. In the rat, the plasma clearance of the four DADS analogs was slower than that of hippuran. In rats with tubular damage induced by cisplatin, the difference in renal retention at 1 hr compared to controls was much greater with hippuran than with the DADS compounds. In the dog, there was marked hepatic retention of the four DADS compounds. In volunteers, serial posterior images obtained with these [99mTc]DADS complexes showed significant hepatic as well as renal activity. The 1-hr plasma clearance and urinary excretion were much lower than with simultaneously injected hippuran. Although these 99mTc agents are satisfactory for imaging the kidneys, they closely mimic the biodistribution of hippuran only in the rabbit, and not in the rat, dog, or man.
D000818:Animals; D004285:Dogs; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005029:Ethylenediamines / Q000378:metabolism; D006801:Humans; D007465:Iodohippuric Acid / Q000378:metabolism; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism; D008253:Macaca mulatta; D015609:Organotechnetium Compounds; D011817:Rabbits; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D013667:Technetium / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D005029:Ethylenediamines; D015609:Organotechnetium Compounds; D007465:Iodohippuric Acid; D013667:Technetium; C028923:technetium Tc 99m N,N'-bis(mercaptoacetamido)ethylenediamine