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

Abstract

This report describes the (99m)Tc labeling of a HYNIC-conjugated vitronectin receptor antagonist (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]). The ternary ligand complex [(99m)Tc(SQ168)(tricine)(TPPTS)] (RP593) was prepared using a non-SnCl(2)-containing formulation. The corresponding (99)Tc analogue, [(99)Tc]RP593, was also prepared and characterized by HPLC and LC-MS. A HPLC concordance experiment using RP593 and [(99)Tc]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, [(99)Tc]RP593 was shown to have comparable binding affinity for the vitronectin receptor to that of SQ168 itself.

64Cu-Labeled Tetrameric and Octameric RGD Peptides for Small-Animal PET of Tumor v 3 Integrin Expression

“…These RGD multimers showed high integrin A variety of radiolabeled peptides has been evaluated for tumor localization and therapy (15,16,20,21,23,32,35). Radiolabeled RGD peptides are of particular interest because they bind to integrin a v b 3 , which is overexpressed on newly formed blood vessels and the cells of many common cancer types.…”

“…Significant progress has also been made in the development of radiolabeled RGD-containing peptides to target integrin a v b 3 overexpressed in various tumors (12)(13)(14)(15)(16)(17). We and others have found that multimeric RGD peptides can significantly enhance the affinity of the receptor-ligand interaction through the polyvalency effect (13,(18)(19)(20)(21)(22)(23). Recent reports on the use of multimeric RGD peptides for ligand endocytosis, imaging of angiogenesis, and targeting of tumors have demonstrated that polyvalency is an efficient strategy for discovering and developing novel RGD-based compounds with better targeting capability and higher cellular uptake because of the increased integrin recognition ability (24)(25)(26)(27).…”

Impact of PKM Linkers on Biodistribution Characteristics of the 99mTc-Labeled Cyclic RGDfK Dimer

“…For the last several years, we and others have been using multimeric cyclic RGD peptides, such as E[c(RGDfK)] 2 (SU016), to develop integrin α v β 3 -targeted radiotracers for imaging rapidly growing and metastatic tumors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The RGD peptide serves as "vehicles" to carry radionuclide ( 99m Tc, 18 F and 64 Cu) to the integrin α v β 3 overexpressed on tumor cells and activated endothelial cells of the tumor neovasculature.…”

Coligand effects on the solution stability, biodistribution and metabolism of the 99mTc-labeled cyclic RGDfK tetramer

“…For the last decade, we have been using ternary ligand systems (HYNIC, tricine, water soluble phosphine or pyridine analog) for 99m Tc-labeling of small biomolecules, including chemotactic peptides [40] and LTB 4 antagonists [41,42] for imaging infection/inflammation, integrin α v β 3 antagonists for tumor imaging [27][28][29][30], and a GPIIb/IIIa antagonist for imaging thrombosis [43][44][45][46]. Regardless of the biomolecule, the Tc:HYNIC:L:tricine ratio in [ 99m Tc(HYNIC-biomolecule)(tricine)(L)] always remains 1:1:1:1 as demonstrated via mixed ligand experiments at the tracer level [43,44], and has been further confirmed by the LC-MS data of [ 99m Tc(HYNIC-biomolecule)(tricine)(L)] (L = TPPTS and ISONIC) at both macroscopic and tracer levels [47,48].…”

“…We and others have been using multimeric cyclic RGD peptides to develop the integrin α v β 3 -targeted radiotracers to image rapidly growing and metastatic tumors in several tumor-bearing animal models [27][28][29][30][31][32][33][34][35][36][37][38][39]. The RGD peptides serve as the targeting biomolecules to carry radionuclide (e.g.…”