Implementation of Multi-Curie Production of (99m)Tc by Conventional Medical Cyclotrons.

UNLABELLED: (99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron. METHODS: A new target system was designed for (99m)Tc production. Target plates made of tantalum were coated with a layer of (100)Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. (99m)Tc was purified by solid-phase extraction or biphasic exchange chromatography. RESULTS: Between 1.04 and 1.5 g of (100)Mo were deposited on the tantalum plates. After high-temperature sintering, the (100)Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1-6.9 h at 20-240 µA of proton beam current, producing up to 348 GBq (9.4 Ci) of (99m)Tc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits. CONCLUSION: The direct production of (99m)Tc via proton bombardment of (100)Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets.

Radiosynthesis of N-[(11)C]-methyl-hydroxyfasudil as a new potential PET radiotracer for rho-kinases (ROCKs).

N-[(11)C]-methyl-hydroxyfasudil was synthesized as a new potential radiotracer for rho-kinases (ROCKs) via a two-step one-pot radiosynthesis. The first step was the methylation of the precursor N-Boc-hydroxyfasudil-sodium salt/benzo-15-crown-5 complex with [(11)C]methyl iodide. The second step involved deprotection of the tert-butoxycarbonyl protecting group. The radiochemical and chemical purities of N-[(11)C]-methyl-hydroxyfasudil were >95% and specific radioactivity was 1565-2565mCi/mumol at the end of the synthesis.

Studies of the mechanism of the in-loop synthesis of radiopharmaceuticals.

A series of experiments were performed to better understand the mechanism of the In-loop [11C]CH3I-methylation. The timing of [11C]CH3I delivery is critical for the high yield of radiolabeling since in-loop radioactivity trapping is reversible. Trapped radioactivity escapes faster from a Tefzel loop compared to a PEEK- or stainless steel loop. Up to 50% of delivered radioactivity may be concentrated at the loop origin (representing 8.1% of the total loop volume). A five-fold reduction of the reaction solvent volume and/or precursor amount may lead to a decrease of the product radiochemical yield either by lowering the in-loop radioactivity trapping or by diminishing conversion of [11C]CH3I into the product.

Improved yields for the in situ production of [11C]CH4 using a niobium target chamber.

The in situ production of [11C]CH4 using a niobium metal target chamber is described. Improved yields are observed in comparison to the previously reported aluminum conical target under similar conditions of beam energy and current. An empirical expression is proposed that quantifies the loss of yield as a function of irradiation time.