Synthesis and biodistribution studies of technetium-99m-labeled aminopeptidase N inhibitor conjugates.
Probestin is a potent aminopeptidase N (APN) inhibitor. Four probestin conjugates containing a tripeptide chelator (N(3)S) and a PEG(2) linker were synthesized and radiolabeled with Tc-99m. The number of -COOH groups on the chelator was altered to increase the excretion of the radiotracer from blood stream via the renal-urinary pathway and to decrease its hepatobiliary uptake. Biodistribution of the radiolabeled conjugates was evaluated in healthy CF-1™ mice at 1h post-injection. The results revealed that the Tc-99m labeled probestin conjugate preferentially (>85% injected dose) excreted via the renal route when an aspartic acid residue was added to the linker (conjugate 4). These results suggest that the pharmacokinetic properties of probestin-based APN-targeted agents could be optimized by adding an appropriate amino acid residue in between the linker and the payload.
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Gopal
G
Pathuri
Andria F
AF
Hedrick
Bryan C
BC
Disch
Michael A
MA
Ihnat
Vibhudutta
V
Awasthi
Hariprasad
H
Gali
D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D051379:Mice; D015394:Molecular Structure; D009928:Organ Specificity; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013667:Technetium / Q000737:chemistry*
D011480:Protease Inhibitors; D013667:Technetium; D018826:CD13 Antigens