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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.

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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.

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The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga–DOTA–NT and 177Lu–DOTA–NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga–DOTA–NT and 48 h for 177Lu–DOTA–NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga–DOTA–NT, the amount of non-specific binding of neurotensin and the effect of 177Lu–DOTA–NT on HT–29 cells. In vivo biodistribution of 68Ga–DOTA–NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu–DOTA–NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.

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