^99mTc-Labeling of a Hydrazinonicotinamide-Conjugated Vitronectin Receptor Antagonist Useful for Imaging Tumors

This report describes the Tc-99m labeling of a HYNIC-conjugated vitronectin receptor antagonist (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Aspo-Phe})-cyclo {Lys-Arg-Gly-Asp-D-Phe}). The ternary ligand complex [Tc-99m(SQ168)(tricine)(TPPTS)] (RP593) was prepared using a non-SnCl2-containing formulation. The corresponding Tc-99 analogue, [Tc-99]RP593, was also prepared and characterized by HPLC and LC-MS. A HPLC concordance experiment using RP593 and [Tc-99]RP593 showed that the same technetium complex was prepared at both the tracer and macroscopic levels. The LC-MS data is completely consistent with the 1:1:1:1 composition for Tc:SQ168:tricine:TPPTS and provides direct evidence that the two radiometric peaks in the radio-HPLC chromatogram of RP593 are indeed due to the resolution of diastereomers. In an in vitro receptor binding assay, [Tc-99]RP593 was shown to have comparable binding affinity for the vitronectin receptor to that of SQ168 itself.