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A system and process for the photo-nuclear production of 67Cu using mainly the 71Ga (γ, α)67Cu reaction. The system and process uses a high energy electron beam, with or without a radiator, in order to isotopically convert at least a portion of a liquid 71Ga target to 67Cu.
A target unit for producing Cu67 radioisotope is described herein, and comprises a cage body releasably coupled to a screw-on cap; and a ceramic capsule containing a solid Zn68 target ingot and having one open end and one closed end and defining an interior chamber for the target ingot. The ceramic capsule is releasably contained between the cage body and the screw-on cap with a lid disposed on the open end of the capsule and a washer positioned between the lid and the screw-on cap. The screw-on cap and the washer provide a water-tight seal between the lid and the capsule. The interior of the capsule is in intimate physical contact with the target ingot; and the Zn68 of the target ingot is free of traces of residual oxygen that interfere with contact of the Zn68 to the capsule.
Altered extracellular proteolysis has been exploited to selectively activate therapeutics in diseases such as cancer; however, once activated, extracellular drugs can diffuse away, limiting efficacy. We address this challenge by coupling proteolytic activation with membrane tethering to retain drugs within diseased tissue. To accomplish this, we developed “restricted interaction peptides” (RIPs), a delivery platform that leverages elevated proteolytic activity to activate membrane-interacting peptides, localizing cargos near the site of proteolysis. We demonstrate that RIPs can deliver diverse therapeutic cargos, including cytotoxins and radioisotopes. As proof of concept, we engineered “FRIP,” a RIP designed for cleavage by fibroblast activation protein (FAP), an endoprotease upregulated in solid tumors and fibrosis. Efficient P4–P4’ substrate sequences were identified and incorporated into FRIPs. Cell-based studies showed that, upon activation, the peptide adhered to membranes rapidly internalized and successfully delivered therapeutic cargos. Consistent with this, FRIPs delivering MMAE inhibited proliferation in an FAP-dependent manner. Imaging studies confirmed tumor targeting with minimal uptake in normal tissues. Finally, FRIPs delivering MMAE or Cu-67 exhibited potent antitumor effects. These findings establish membrane tethering as a strategy to enhance drug retention.
The half-life of 67 Cu was determined through serial gamma-ray spectrometry measurements of the dominant gamma emission (E γ : 184.6 keV; branching ratio: 48.7%) produced following β- decay. Data were collected consecutively for 1000 s per measurement, with a total of 3063 measurements over the duration of 36 days. The incidence rate for the 184.6 keV gamma-ray was determined from the spectral peak area and duration of each measurement. This rate was then corrected to account for detector dead-time, radioactive decay during each acquisition and drift in the computer clock in comparison to NIST nuclear clock. Least-squares regression analysis was performed to determine the half-life of 67 Cu. The result was 61.761 ± 0.004 h, which is the highest precision measurement to date, and marks a 24-fold precision improvement over the current Nuclear Data Sheets value.
Is the 67 Cu production worldwide feasible for expanding preclinical and clinical studies? How can we face the ingrowing demands of this emerging and promising theranostic radionuclide for personalized therapies? This review looks at the different production routes, including the accelerator- and reactor-based ones, providing a comprehensive overview of the actual 67 Cu supply, with brief insight into its use in non-clinical and clinical studies. In addition to the most often explored nuclear reactions, this work focuses on the 67 Cu separation and purification techniques, as well as the target material recovery procedures that are mandatory for the economic sustainability of the production cycle. The quality aspects, such as radiochemical, chemical, and radionuclidic purity, with particular attention to the coproduction of the counterpart 64 Cu, are also taken into account, with detailed comparisons among the different production routes. Future possibilities related to new infrastructures are included in this work, as well as new developments on the radiopharmaceuticals aspects.