⁴⁷ Sc is one of the most promising theranostic radionuclides, thanks to its low energy γ -ray emission (159 keV), suitable for single photon emission computed tomography imaging and its intense β ⁻ emission, useful for tumour treatment. Despite promising preclinical results, the translation of ⁴⁷ Sc-therapeutic agents to the clinic is hampered by its limited availability. Among different ⁴⁷ Sc-production routes currently being investigated, the ^nat V(p,x) ⁴⁷ Sc reaction has proved to be of particular interest, thanks to the low-cost and easy availability on the market of ^nat V material and the diffusion of medium energy proton cyclotrons. However, the cross section of this specific nuclear reaction is quite low and small amounts of Sc-contaminants are co-produced at energies E _P ≤ 45 MeV, namely ⁴⁸ Sc and ⁴⁶ Sc. The main concern with these Sc-contaminants is their contribution to the patient absorbed dose. For such a reason, the absorbed dose contributions to healthy organs and the effective dose contributions by the three radioisotopes, ⁴⁸ Sc, ⁴⁷ Sc and ⁴⁶ Sc, were evaluated using DOTA-folate conjugate (cm10) as an example of radiopharmaceutical product. Considering as acceptable the limits of 99% for the radionuclidic purity and 10% for the contribution of radioactive Sc-contaminants to the total effective dose after ⁴⁷ Sc-cm10 injection, it was obtained that proton beam energies below 35 MeV must be used to produce ⁴⁷ Sc through irradiation of a ^nat V target.

Purpose: ⁶⁴Cu and ⁶⁷Cu radioisotopes have nuclear characteristics suitable for nuclear medicine applications. The production of ⁶⁴Cu is already well established. However, the production of ⁶⁷Cu in quantities suitable to conduct clinical trials is more challenging as it leads to the coproduction of other Cu isotopes, in particular ⁶⁴Cu. The aim of this study is to investigate the possibility of using a CuCl₂ solution with a mixture of ^67/64Cu radioisotopes for therapeutic purposes, providing an alternative solution for the cyclotron production problem.Methods: Copper radioisotopes activities were calculated by considering proton beam irradiation of the following targets: (i) ⁷⁰Zn in the energy range 70–45 MeV; (ii) ⁶⁸Zn in the energy range 70–35 MeV; (iii) a combination of ⁷⁰Zn (70–55 MeV) and ⁶⁸Zn (55–35 MeV). The contribution of each copper radioisotope to the human‐absorbed dose was estimated with OLINDA/EXM software using the biokinetic model for CuCl₂ published by ICRP 53. The total absorbed dose generated by the ^67/64CuCl₂ mixture, obtained through different production routes, was calculated at different times after the end of the bombardment (EOB). A simple spherical model was used to simulate tumors of different sizes containing uniformly distributed ^67/64Cu mixture and to calculate the absorbed dose of self‐irradiation. The biological damage produced by ⁶⁷Cu and ⁶⁴Cu was also evaluated through cellular dosimetry and cell surviving fraction assessment using the MIRDcell code, considering two prostate cancer cell lines with different radiosensitivity.Results: The absorbed dose to healthy organs and the effective dose (ED) per unit of administered activity of ⁶⁷CuCl₂ are higher than those of ⁶⁴CuCl₂. Absorbed dose values per unit of administered activity of ^67/64CuCl₂ mixture increase with time after the EOB because the amount of ⁶⁷Cu in the mixture increases. Survival data showed that the biological damage caused per each decay of ⁶⁷Cu is greater than that of ⁶⁴Cu, assuming that radionuclides remain accumulated in the cell cytoplasm. Sphere model calculations demonstrated that ⁶⁴Cu administered activity must be about five times higher than that of ⁶⁷Cu to obtain the same absorbed dose for tumor mass between 0.01 and 10 g and about 10 times higher for very small spheres. Consequently, the ⁶⁴CuCl₂‐absorbed dose to healthy organs will reach higher values than those of ⁶⁷CuCl₂. The supplemental activity of the ^67/64CuCl₂ mixture, required to get the same tumor‐absorbed dose produced by ⁶⁷CuCl₂, triggers a dose increment (DI) in healthy organs. The waiting time post‐EOB necessary to keep this DI below 10% (t_10%) depends on the irradiation methods employed for the production of the ^67/64CuCl₂ mixture.Conclusions: A mixture of cyclotron produced ^67/64Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl₂ with minimal DI to healthy organs compared with pure ⁶⁷Cu. Irradiation of a ⁷⁰Zn+⁶⁸Zn target in the 70–35 MeV proton energy range for 185 h appears to be the best option from among all the production routes investigated, as it gives the maximum amount of activity, the shortest t_10% (10 h), and less than 1% of ⁶¹Cu and ⁶⁰Cu impurities.

Actinium-225 and other alpha-particle-emitting radionuclides have shown high potential for cancer treatment. Reconstituted high-density lipoproteins (rHDL) specifically recognize the scavenger receptor B type I (SR-BI) overexpressed in several types of cancer cells. Furthermore, after rHDL-SR-BI recognition, the rHDL content is injected into the cell cytoplasm. This research aimed to prepare a targeted ²²⁵Ac-delivering nanosystem by encapsulating the radionuclide into rHDL nanoparticles. The synthesis of rHDL was performed in two steps using the microfluidic synthesis method for the subsequent encapsulation of ²²⁵Ac, previously complexed to a lipophilic molecule (²²⁵Ac-DOTA-benzene-p-SCN, CLog P = 3.42). The nanosystem (13 nm particle size) showed a radiochemical purity higher than 99% and stability in human serum. In vitro studies in HEP-G2 and PC-3 cancer cells (SR-BI positive) demonstrated that ²²⁵Ac was successfully internalized into the cytoplasm of cells, delivering high radiation doses to cell nuclei (107 Gy to PC-3 and 161 Gy to HEP-G2 nuclei at 24 h), resulting in a significant decrease in cell viability down to 3.22 ± 0.72% for the PC-3 and to 1.79 ± 0.23% for HEP-G2 at 192 h after ²²⁵Ac-rHDL treatment. After intratumoral ²²⁵Ac-rHDL administration in mice bearing HEP-G2 tumors, the biokinetic profile showed significant retention of radioactivity in the tumor masses (90.16 ± 2.52% of the injected activity), which generated ablative radiation doses (649 Gy/MBq). The results demonstrated adequate properties of rHDL as a stable carrier for selective deposition of ²²⁵Ac within cancer cells overexpressing SR-BI. The results obtained in this research justify further preclinical studies, designed to evaluate the therapeutic efficacy of the ²²⁵Ac-rHDL system for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor.

Background: ¹⁵⁵Tb represents a potentially useful radionuclide for diagnostic medical applications, but its production remains a challenging problem, in spite of the fact that many production routes have been already investigated and tested. A recent experimental campaign, conducted with low-energy proton beams impinging on a ¹⁵⁵Gd target with 91.9% enrichment, demonstrated a significant co-production of ^156gTb, a contaminant of great concern since its half-life is comparable to that of ¹⁵⁵Tb and its high-energy γ emissions severely impact on the dose released and on the quality of the SPECT images. In the present investigation, the isotopic purity of the enriched ¹⁵⁵Gd target necessary to minimize the co-production of contaminant radioisotopes, in particular ^156gTb, was explored using various computational simulations. Results: Starting from the recent experimental data obtained with a 91.9% ¹⁵⁵Gd-enriched target, the co-production of other Tb radioisotopes besides ¹⁵⁵Tb has been theoretically evaluated using the Talys code. It was found that ¹⁵⁶Gd, with an isotopic content of 5.87%, was the principal contributor to the co-production of ^156gTb. The analysis also demonstrated that the maximum amount of ¹⁵⁶Gd admissible for ¹⁵⁵Tb production with a radionuclidic purity higher than 99% was 1%. A less stringent condition was obtained through computational dosimetry analysis, suggesting that a 2% content of ¹⁵⁶Gd in the target can be tolerated to limit the dose increase to the patient below the 10% limit. Moreover, it has been demonstrated that the imaging properties of the produced ¹⁵⁵Tb are not severely affected by this level of impurity in the target. Conclusions: ¹⁵⁵Tb can be produced with a quality suitable for medical applications using low-energy proton beams and ¹⁵⁵Gd-enriched targets, if the ¹⁵⁶Gd impurity content does not exceed 2%. Under these conditions, the dose increase due to the presence of contaminant radioisotopes remains below the 10% limit and good quality images, comparable to those of ¹¹¹In, are guaranteed.

A multi-element tissue-equivalent proportional counter (TEPC), based on a single gas electron multiplier (GEM) foil of standard geometry, has been constructed with 16 cylindrical sensitives volumes. In this article, the design of this novel counter is described and first microdosimetric measurements are presented. To study the response of the GEM-TEPC to both low and high linear energy transfer radiation fields, the microdosimetric spectra due to a ¹³⁷Cs gamma-ray source and to fast neutrons from ⁷Li(d,n)⁸Be reaction have been measured using pure propane gas at low pressure, in order to simulate a tissue site of about 1 µm equivalent size. The comparison with spectra measured with a spherical TEPC and with a mini-TEPC demonstrates promising properties for application of the GEM-TEPC for microdosimetric applications.