Targeted alpha‐therapy (TAT) has great potential for treating a broad range of late‐stage cancers by delivering a focused and lethal radiation dose to tumors. Actinium‐225 (225Ac) is an emerging alpha emitter suitable for TAT; however, the availability of chelators for Ac remains limited to a small number of examples (DOTA and macropa). Herein, we report a new Ac macrocyclic chelator named ‘crown’, which binds quantitatively and rapidly (<10 min) to Ac at ambient temperature. We synthesized 225Ac‐crown‐αMSH, a peptide targeting the melanocortin 1 receptor (MC1R), specifically expressed in primary and metastatic melanoma. Biodistribution of 225Ac‐crown‐αMSH showed favorable tumor‐to‐background ratios at 2 h post injection in a preclinical model. In addition, we demonstrated dramatically different biodistrubution patterns of 225Ac‐crown‐αMSH when subjected to different latency times before injection. A combined quality control methodology involving HPLC, gamma spectroscopy and radioTLC is recommended.

A series of 15 water-soluble titanocene dichloride derivatives containing alkylammonium groups pendant to one (monocationic complexes) or both (dicationic complexes) cyclopentadienyl rings has been synthesized and characterized. The in vitro cytotoxicities of this small library of potential anticancer drugs have been assessed against human lung cancer (H209, A549, H209/CP) and ovarian cancer (A2780, A2780/CP) cell lines, and the results are compared with the cytotoxicities of both cisplatin (cis-PtCl 2 (NH 3 ) 2 ) and a clinical formulation of titanocene dichloride that is commonly used against cisplatin-resistant tumors. While none of the compounds exhibit potency greater than that of cisplatin, several are clearly superior to the clinical formulation. In particular dicationic complexes generally exhibit greater potency than do the corresponding monocationic analogues, and derivatives containing protonated piperidinyl rings exhibit greater potency than do compounds containing protonated 2-aminoethyl or 3-aminopropyl groups. Eight of the compounds, representing a wide range of potencies, were characterized crystallographically but no correlations between effectiveness and structures were obvious.

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Microwave heating was used to prepare eta5-rhenium carborane complexes in aqueous reaction media. For carboranes bearing sterically demanding substituents, isomerization of the cage from 3,1,2 to 2,1,8 derivatives occurred concomitantly with complexation. Microwave heating was equally effective at the tracer level using technetium-99m, affording access to a new class of synthons for designing novel molecular imaging agents.

Recent clinical results have demonstrated remarkable treatment responses of late-stage cancer patients when treated with alpha-emitting radionuclides such as actinium-225 ( 225 Ac). The resulting intense global effort to produce greater quantities of 225 Ac has triggered a number of emerging technologies to produce this rare, yet important, radionuclide. Accelerator-based methods for increasing global 225 Ac production capacity have focused on the high energy (>100 MeV) proton irradiation of thorium, despite the coproduction of the undesirable 227 Ac byproduct at 0.1−0.3% of the 225Ac activity. We at TRIUMF have developed a process for the production of a 225 Ra/ 225 Ac generator from irradiated thorium that results in an 225 Ac product with reduced 227 Ac content. 225 Ac was separated from irradiated thorium and coproduced radioactive spallation and fission products using a thorium peroxide precipitation method followed by cation exchange and extraction chromatography. Stable and radioactive tracer studies demonstrated the ability of this method to separate Ac from most other elements, providing a directly produced Ac product with measured 227 Ac content of (0.15 ± 0.04)%. A second, indirectly produced Ac product with 227 Ac content of <7.5 × 10 −5 % is obtained by repeating the final extraction chromatography step with the 225 Racontaining fraction. The 225 Ra-derived 225 Ac showed similar or improved quality compared to the initial, directly produced 225 Ac product in terms of chemical purity and radiolabeling capability, the latter of which was comparable with other 225 Ac sources reported in the literature.