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 (N3S) and a PEG2 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 1 h 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.

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