Unstable isotopes and their capacity to emit ionizing radiation have been employed in clinical practice not only for diagnostic, but also for therapeutic purposes, with significant contribution in several fields of medicine and primarily in the management of oncologic patients. Their efficacy is associated with their ability to provide the targeted delivery of ionizing radiation for a determined duration. These compounds can be used for curative or palliative treatment, as well as for a diagnostic‑therapeutic (theranostic) approach. This review summarises the most recent trends in radionuclide treatment for several malignancies, including prostate cancer, neuroendocrine tumours, and hematological and thyroid malignancies, in which radionuclide‑based therapies have been employed with high effectiveness.

Copper, a cofactor for many enzymes, is a bioelement that is involved in many main biochemical processes; although high levels of copper promote the proliferation of cancer cells. Further development of radiopharmaceuticals based on copper radioisotopes depend on understanding and taking advantage of its biochemical pathways in oncogenesis. As with other radiometals used in molecular imaging and/or targeted therapy, biological vectors are employed to transport copper radioisotopes to a target, aiming for high specific uptake at tumor sites and precise delivery of ionizing radiation. Evidence of the clinical utility of copper radioisotopes in the ionic form CuCl₂ were also proven in an in vivo study of the copper metabolism, guiding personalized copper-chelating treatment in cancer patients and in imaging pathological sites associated with copper imbalance. Five of the copper radioisotopes have gained interest for nuclear medicine applications, based on their emissions, energies, and half-lives, as they can be produced with pharmaceutical-grade quality. The uptake mechanism, kinetics, and metabolic parameters are important findings in molecular imaging, which are decisive when designing individualized targeted radiotherapy for dose calculations of high linear energy transfer Auger electrons and β⁻ emissions of ⁶⁴Cu and ⁶⁷Cu. As radiation deposits a high amount of energy within the intra-cellular space, the biochemical involvement of copper determines targets in drug design and validation. The biochemical pathways depict copper metabolism in normal cells and highlight its increased activity in tumor progression and angiogenesis. The avid uptake of copper into inter- and intra-mitochondrial spaces, as constituents of cytochrome C oxidase, substantiate the selection of ^64/67CuCl₂ as theranostic agents.

⁶⁴Cu is a cyclotron-produced radionuclide suitable for positron emission tomography (PET) and internal radiotherapy. We have been focused on ⁶⁴Cu radioisotope due to its favorable nuclear characteristics (β⁺ emission, 18% and β⁻ emission, 39%). Moreover, the electron capture (43%) implies Auger electron emission with high linear energy transfer in the targeted cells. Also, the 12.7 hours half-life allows a good uptake and distribution of the radiopharmaceuticals to obtain qualitative images with high contrast. The production of no-carrier-added ⁶⁴Cu via the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction using a variable energy cyclotron (TR-19, ACSI, Canada) was studied in our work involving the implementation of a fully automated solid target irradiation and processing system. In this paper we report the validation of the process for the automated production and purification of ⁶⁴Cu produced in a variable energy (14-19 MeV) cyclotron, using a commercially available automated solid target system (ALCEO, Comecer S.p.A, Italy), comprising modules for electrodeposition, pneumatic transfer, irradiation unit, dissolving and purification. The obtained ⁶⁴CuCl₂ solution complies with the requirements of a radiopharmaceutical for medical applications. The process is to be translated for production of other copper radioisotopes of medical interest.

Recent advances and large-scale use of hybrid imaging modalities like PET-CT have led to the necessity of improving nano-drug carriers that can facilitate both functional and metabolic screening in nuclear medicine applications. In this study, we focused on the evaluation of four potential imaging nanoparticle structures labelled with the ⁶⁸Ga positron emitter. For this purpose, we functionalized NHS-activated PEG-gold nanoparticles with ⁶⁸Ga-DOTA-Neuromedin B, ⁶⁸Ga-DOTA-PEG(4)-BBN(7-14), ⁶⁸Ga-DOTA-NT and ⁶⁸Ga-DOTA-Neuromedin N. In vitro binding kinetics and specific binding to human HT-29 colon carcinoma cells and DU-145 prostate carcinoma cells respectively were assessed, over 75% retention being obtained in the case of ⁶⁸Ga-DOTA-PEG(4)-BBN(7-14)-AuNP in prostate tumour cells and over 50% in colon carcinoma cells. Biodistribution in NU/J mice highlighted a three-fold uptake increase in tumours at 30 min post-injection of ⁶⁸Ga-DOTA-NT-AuNP and ⁶⁸Ga-DOTA-PEG(4)-BBN(7-14)-AuNP compared to ⁶⁸Ga-DOTA-NT and ⁶⁸Ga-DOTA-PEG(4)-BBN(7-14) respectively, therewith fast distribution in prostate and colon tumours and minimum accumulation in non-targeted tissues.