Dataset Information

Cyclotron-Based Production of ⁶⁷Cu for Radionuclide Theranostics via the ⁷⁰Zn(p,α)⁶⁷Cu Reaction.

ABSTRACT: Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although ⁶¹Cu and ⁶⁴Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart ⁶⁷Cu plays a key role for further radiopharmaceutical development in the future. Until now, the ⁶⁷Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added ⁶⁷Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the ⁷⁰Zn(p,α)⁶⁷Cu reaction. With this purpose, proton irradiation of electrodeposited ⁷⁰Zn targets was performed followed by two-step radiochemical separation based on solid-phase extraction. Activities of up to 600MBq ⁶⁷Cu at end of bombardment, with radionuclidic purities over 99.5% and apparent molar activities of up to 80MBq/nmol, were quantified.

SUBMITTER: Bruhlmann SA

PROVIDER: S-EPMC9961624 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Cyclotron-Based Production of 67Cu for Radionuclide Theranostics via the 70Zn(p,α)67Cu Reaction.

Brühlmann Santiago Andrés SA Walther Martin M Kreller Martin M Reissig Falco F Pietzsch Hans-Jürgen HJ Kniess Torsten T Kopka Klaus K

Pharmaceuticals (Basel, Switzerland) 20230217 2

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although 61Cu and 64Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart 67Cu plays a key role for further radiopharmaceutical development in the future. Until now, the 67Cu shortage has not been solved; however, different p ...[more]

PMID: 37259458

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Project description:Somatostatin type 2 receptor (SSTR2) radionuclide therapy using β- particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [177Lu]Lu‑DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionuclides. Consequently, this study evaluates the pharmacokinetic effects of the albumin-binding domain cLAB4 on theranostic performance of copper‑67-labeled NODAGA-TATE variants in an SSTR2-positive mouse pheochromocytoma (MPC) model. Methods: Binding, uptake, and release of radioligands as well as growth-inhibiting effects were characterized in cells grown as monolayers and spheroids. Tissue pharmacokinetics, absorbed tumor doses, and projected human organ doses were determined from quantitative SPECT imaging in a subcutaneous tumor allograft mouse model. Treatment effects on tumor growth, leukocyte numbers, and renal albumin excretion were assessed. Results: Both copper‑64- and copper‑67-labeled versions of NODAGA-TATE and NODAGA-cLAB4‑TATE showed similar SSTR2 binding affinity, but faster release from tumor cells compared to the clinical reference [177Lu]Lu‑DOTA-TATE. The bifunctional SSTR2/albumin-binding radioligand [67Cu]Cu‑NODAGA-cLAB4‑TATE showed both an improved uptake and prolonged residence time in tumors resulting in equivalent treatment efficacy to [177Lu]Lu‑DOTA-TATE. Absorbed doses were well tolerated in terms of leukocyte counts and kidney function. Conclusion: This preclinical study demonstrates therapeutic efficacy of [67Cu]Cu‑NODAGA-cLAB4‑TATE in SSTR2-positive tumors. As an intrinsic radionuclide theranostic agent, the radioligand provides stable radiocopper complexes and high sensitivity in SPECT imaging for prospective determination and monitoring of therapeutic doses in vivo. Beyond that, copper‑64- and copper‑61-labeled versions offer possibilities for pre- and post-therapeutic PET. Therefore, NODAGA-cLAB4-TATE has the potential to advance clinical use of radiocopper in SSTR2-targeted cancer theranostics.

Dataset Information

Cyclotron-Based Production of ⁶⁷Cu for Radionuclide Theranostics via the ⁷⁰Zn(p,α)⁶⁷Cu Reaction.

Publications

Cyclotron-Based Production of <sup>67</sup>Cu for Radionuclide Theranostics via the <sup>70</sup>Zn(p,α)<sup>67</sup>Cu Reaction.

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