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The chemical reactivity of the metal fragment [Tc(N)(PXP))](super 2+), composed by a diphosphine ligand (PXP) coordinated to a [Tc(super V)(N)](super 2+) core, is described. It is concluded that the novel metal fragment fac-[M(N)(PXP)](super 2+) could be utilized as an efficient synthon for the preparation of a large class of asymmetrical, nitrido heterocomplexes incorporating a particular diphosphine ligand and a variety of bidentate chelating molecules.

Abstract: Introduction: Tetradentate acyclic and macrocyclic diphosphine ligands (P2N2 and P2S2) have been synthesized and characterized as potential chelates for Rh(III). Methods: The coordination complexes [RhCl2(L1)]Cl, trans-[RhCl2(L2)]PF6, [Ni(L2)](PF6)2, [Ni(L3)](PF6)2, [RhCl2(L4)]PF6 and [RhCl2(L5)]PF6 have been synthesized and characterized. In addition, radiochemistry studies of the 105Rh complexes with the ligands N,N′-bis[2-(diphenylphosphino)phenyl]-1,3-diaminopropane (L1), 4,8-diphenyl-1,11-diaza-4,8-diphosphaundecane (L2), 5,9-diphenyl-5,9-diphospha-2,12-dithiatridecane (L3) and 1,4,8,11-tetraphenyl-4,8-diphospha-1,11-dithiaundecane (L4) are reported, including normal mouse biodistributions of 105Rh–L2. Results: trans-[RhCl2(L2)]PF6 crystallized in the monoclinic space group P21/c with a=9.9353(5) Å, b=9.0929(5) Å, c=28.689(1) Å, β=93.1400(10) deg, Z=4, R=0.037 and R w=0.053. [Ni(L2)](PF6)2 crystallized in the monoclinic space group P21/c with a=11.9665(6) Å, b=14.8903(7) Å, c=31.148(1) Å, β=91.587(1) deg, Z=8, R=0.056 and R w=0.083. μ-O2SO2-[Ni(L5)]2(PF6)2, an unusual sulfate-bridged Ni(II) dimer, crystallized in the triclinic space group P1 bar with a=15.179(2) Å, b=15.514(2) Å, c=16.128(2) Å, α=105.280(7) deg, β=113.074(6) deg, γ=101.657(8) deg, Z=2, R=0.050 and R w=0.072. Conclusions: Phosphine-containing ligands allowed for lower temperatures and lower ethanol concentrations in the formulations for 105Rh(L) complexation, but at the expense of higher ligand concentrations. [ABSTRACT FROM AUTHOR]

Abstract: Ga-AMBA (Ga-DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R). Syntheses for natGa-AMBA, [67Ga]Ga-AMBA and [68Ga]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [68Ga]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated 68Ge/68Ga generator elution and purification. The total synthesis time, including the fractional elution of the generator, was 20min for Sep-Pak purified material and 40min for HPLC-purified [68Ga]Ga-AMBA. Both [67Ga]Ga-AMBA and [177Lu]Lu-AMBA showed comparable high affinity for GRP-R in the human prostate cancer cell line PC-3 in vitro (k D=0.46±0.07; 0.44±0.08nM), high internalization (78; 77%) and low efflux from cells at 2h (2.4±0.7; 2.9±1.8%). Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [177Lu]Lu-, [111In]In-, [67Ga]Ga- and [68Ga]Ga-AMBA. [Copyright &y& Elsevier]

[sup177]Lu-AMBA (AMBA = DO3A-CH[sub2]CO-G-[4-aminobenzoyl)-QWAVGHLM-NH[sub2]) is being developed for the radio- therapeutic treatment of tumors that express the gastrin-releasing peptide receptor (GRP-R). In this study we investigated the fate of the [sup177]hafnium ([sup177]Hf) that forms upon the decay of [sup177]Lu while the latter is complexed with AMBA. When decayed solutions of [sup177]Lu-AMBA were analyzed, it was found that [sup177]Hf is retained in the DO3A monoamide chelator, forming a pair of interconverting isomers. We report the synthesis and full characterization of [supnat]Lu-AMBA and the studies performed to demonstrate its correspondence to radioactive [sup177]Lu-AMBA. We also report the synthesis and characterization of Hf-AMBA and, by NMR studies, show structural analogies between Hf-AMBA, its parent compound Lu-AMBA, and the unmetallated AMBA ligand. In the NMR spectra of both the metallated and unmetallated AMBA ligand, a stacking interaction between the amino benzoyl residue in the linker and a tryptophan in the truncated bombesin [BBN(7-14)-NH[sub2]] peptide targeting group was found. [ABSTRACT FROM AUTHOR]

Abstract: A robust formulation was developed for [177Lu]Lu-AMBA (177Lu-DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2), a Bombesin-like agonist with high affinity for Gastrin Releasing Peptide (GRP) receptors. During optimization of labeling, the effect of several radiostabilizers was evaluated; a combination of selenomethionine and ascorbic acid showed superiority over other tested radiostabilizers. The resulting two-vial formulation maintains a radiochemical purity (RCP) of >90% for at least 2 days at room temperature. The method of stabilization should be useful for other methionine-containing peptide radiopharmaceuticals in diagnostic and therapeutic applications. [Copyright &y& Elsevier]