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Introduction: Rhenium-186g (t 1/2 = 3.72 d) is a β - emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185 Re(n,γ) 186g Re, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186 W results in a 186g Re product with a higher specific activity, allowing it to be used more broadly for targeted radiotherapy applications. This targets the unmet clinical need for more efficient radiotherapeutics., Methods: A target consisting of highly enriched, pressed 186 WO 3 was irradiated with protons at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF) to evaluate 186g Re product yield and quality. LANL-IPF was operated in a dedicated nominal 40 MeV mode. Alkaline dissolution followed by anion exchange chromatography was used to isolate 186g Re from the target material. Phantom and radiolabeling studies were conducted with the produced 186g Re activity., Results: A 186g Re batch yield of 1.38 ± 0.09 MBq/μAh or 384.9 ± 27.3 MBq/C was obtained after 16.5 h in a 205 μA average/230μA maximum current proton beam. The chemical recovery yield was 93% and radiolabeling was achieved with efficiencies ranging from 60-80%. True specific activity of 186g Re at EOB was determined via ICP-AES and amounted to 0.788 ± 0.089 GBq/μg (0.146 ± 0.017 GBq/nmol), which is approximately seven times higher than the product obtained from neutron capture in a reactor. Phantom studies show similar imaging quality to the gold standard 99m Tc., Conclusions: We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity 186g Re from enriched 186 WO 3 targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope (213)Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi(3+), however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents., Methods: The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), were prepared by a previously reported method and investigated here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[(R)-2-amino-3-(p-isothiocyanato-phenyl)propyl]-trans-(S,S)- cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, (207)Bi (t(1/2)=32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi(3+) and the generator parent ion Ac(3+)., Results: In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi(3+) in the presence of the parent isotope Ac(3+). Among the four tested, L(py) was found to exhibit optimal Bi(3+)-binding kinetics and complex stability. L(py) complexes Bi(3+) more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi(3+) over Ac(3+)., Conclusion: Taken together, these data implicate L(py) as a valuable chelating agent for the delivery of (213)Bi. Its selectivity for Bi(3+) and rapid and stable labeling properties warrant further investigation and biological studies., (Published by Elsevier Inc.)