Multifunctional phosphinimine ligand for 99m-Tc(VII) stabilization [abstract]
Abstract
The preparation of higher oxidation state, in vivo stable, 99mTc(VII) (and
Re(VII)) transition metal complexes bearing biologically active molecules has
recently received considerable attention because of their potential
applications in nuclear medicine and radiopharmacy. In particular, labeling
strategies based on Tc(VII) conjugates would provide attractive prospects for
labeling tumor specific peptides (and other tumor-avid biomolecules) directly
with 99mTcO4
- without the intervention of external reducing agents (e.g.
Sn(II)). Our approach for stabilizing Tc(VII) is based on the utility of
phosphinimine (R3P=NSiMe3) ligand frameworks. In this context, we have
designed a new multidentate phosphinimine ligand framework of the general
formula R'C(R2P=NSiMe3)x (where x=2,3). Herein, we report the synthesis of a
novel tridentate phosphinimine ligand, (CH3C(CH2R2P=NSiMe3)3), P3N3 (1), with
“PN-PN-PN” ligand framework, and their coordination chemistry with [MO4]- (M =
99mTc and Re).
Interaction of multifunctional phosphinimine ligand P3N3 (1) (10-4M) with
generator eluted pertechnatate (1-5mCi) at 250C produced ion-pair of
composition (CH3C(CH2R2P=NH2
+)3(TcO4
-)3) (2) in >98% yields. The ion-pair
((P3N3)+(TcO4)3
-) (2) formed is unequivocally characterized by paper
chromatography and HPLC. The new Tc(VII) phosphinimine complex
((P3N3)+(TcO4)3
-) (2) demonstrated very good stability over 24 hour time
periods in ethanol, water, and HSA. This poster presentation will include
details on the utility of “PN-PN-PN” framework for stabilizing Tc(VII) and in
vitro stability profiles of the technetium complex. These results indicate
that the Tc-phosphinimine ligands may be used in the design and development
of a variety of new 99mTechnetium radiopharmaceuticals in the future.