Labeling a Hydrazino Nicotinamide-Modified Cyclic IIb/IIIa Receptor Antagonist with ^99mTc Using Aminocarboxylates as Coligands

Abstract

A series of 99mTc 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 99mTc 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 (> or = 20,000 mCi/mumol) can be achieved for the complex [99mTc(HYNICtide)(tricine)2] without postlabeling purification. The complex [99mTc(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 [99mTc(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 reacting excess EDDA with [99mTc(HYNICtide)(tricine)2]. The complex [99mTc(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)ethylenediaminetriacetic acid) as coligands. It is clear that the replacement of tricine by other polydentate aminocarboxylates produces 99mTc-HYNICtide complexes with higher stability and fewer coordination isomers.

99mTc-Labeled Duramycin as a Novel Phosphatidylethanolamine-Binding Molecular Probe

“…First, to preserve the convenience of HYNIC radiochemistry we adopted a phosphine compound as a third coligand, as described by Edwards et al (17,18). To this end, although tricine alone has been widely used as a coligand for HYNIC radiochemistry, in which 2 tricine molecules form a well-defined coordination complex with 99m Tc and the hydrazine group of HYNIC, the tricine chelation core is known to be less stable under dilute conditions (17)(18)(19)(20)(21)(22). By including TPPTS in the coordination chemistry, 99m Tc-duramycin remains stable both in solution and in vivo, consistent with the prior findings (17,18).…”

Synthesis and crystal and molecular structure of a tetranuclear cluster based on the rhenium(III)-bisorganohydrazino core: [Re(HNNC4H3N2)(NNC4H3N2)(OCH3)2]4

“…In this latter respect, the chemistry of technetium with 2-hydrazino-nicotinamide derivatized peptides has received considerable attention [4][5][6]. In modeling the chemistry of the Tc-organohydrazino core of these radiopharmaceuticals, we have developed the chemistry of a class of compounds derived from the rhenium bispyridinodiazene core, {Re(η 2 -HNNC 5 H 4 N)(η 1 -NNC 5 H 4 NH)} 3+ , shown schematically [7] (Scheme 1).…”

Radiopharmaceuticals for somatostatin receptor imaging

“…It was assumed that the 99m Tc species is coordinated by two tricine molecules and the terminal N-atom of the hydrazine group of HYNIC in the resulting Tc-HYNIC-protein complex [41]. Detailed HPLC analysis indicated that the complex can reversibly adopt various forms, depending on temperature, reaction time and pH.…”