Labeling a hydrazino nicotinamide-modified cyclic IIb/IIIa receptor antagonist with Tc-99m using aminocarboxylates as coligands

A series of Tc-99m complexes containing a hydrazinonicotinamide-conjugated cyclic IIb/IIIa receptor antagonist, cyclo(D-Val-NMeArg-Gly-Asp-Mamb-(hydrazinonicotinyl-5-(6-aminocaproic acid))), were synthesized in high yield using tricine or other aminocarboxylates as coligands. These Tc-99m complexes have the potential to be used as thrombus imaging agents. The radiolabeling of the HYNIC-conjugated cyclic IIb/IIIa peptide (HYNICtide) was carried out by reaction with pertechnetate in the presence of excess tricine and stannous chloride at pH 4-5. The reaction time and temperature depend on the amount of the HYNICtide and pertechnetate used for the radiolabeling. Very high specific activity (greater than or equal to 20 000 mCi/mu mol) can be achieved for the complex [Tc-99m(HYNICtide)(tricine)(2)] without postlabeling purification. The complex [Tc-99m(HYNICtide)(tricine)(2)] was found by two reversed phase HPLC methods to exist as multiple species, some of which interconvert, depending on the temperature, reaction time, and pH of the reaction mixture. The presence of these multiple species is most likely due to different bonding modalities of either the hydrazine moiety of the HYNICtide or the two tricine coligands. The complex [Tc-99m(HYNICtide)(EDDA)](EDDA = ethylenediamine-N,N'-diacetic acid) was prepared either by reacting the cyclic IIb/IIIa HYNICtide with pertechnetate, excess EDDA, and stannous chloride at pH 4-5 and 75 degrees C for 30 min or by reading excess EDDA with [Tc-99m(HYNICtide)(tricine)(2)]. The complex [Tc-99m(HYNICtide)(EDDA)] was found to be stable for at least 12 h in the reaction mixture. Three major species were detected in the radio-HPLC chromatograms, presumably due to the more limited number of possible coordination isomers. Similar results were obtained using other polydentate aminocarboxylates (such as HEDTA, N-(2-hydroxyethyl)ethylenediaminetriacet acid) as coligands. It is clear that the replacement of tricine by other polydentate aminocarboxylates produces Tc-99m-HYNICtide complexes with higher stability and fewer coordination isomers.