Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

Highly localized radiotherapy with radionuclides is a commonly used treatment modality for patients with unresectable solid tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This uses local intratumoral injection of 5-nm-diameter gold nanoparticles (AuNPs) labeled with an α-emitter (²¹¹At), modified with polyethylene glycol (PEG) chains and attached to HER2-specific monoclonal antibody (trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of gold for heavy halogens, the bioconjugate was labelled with ²¹¹At obtained by α irradiation of the bismuth target. The labeling yield of ²¹¹At was greater than 99%. ²¹¹At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that ²¹¹At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that ²¹¹At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the ²¹¹At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.

⁴⁴Sc is a promising β ⁺-emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc³⁺ to the Lu³⁺ and Y³⁺ cations, ⁴⁴Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the ¹⁷⁷Lu- and ⁹⁰Y-bioconjugates, what is important in planning the radionuclide therapy. ⁴⁴Sc can be obtained from the ⁴⁴ Ti/⁴⁴Sc generator. An alternative method for ⁴⁴Sc production can be the irradiation of ⁴⁴Ca target at small cyclotrons. The aim of our work was to optimize the parameters of ⁴⁴CaCO₃ irradiation and to develop a simple procedure for ⁴⁴Sc separation from the calcium target. For optimization study, ⁴⁴CaCO₃ targets were irradiated by protons in the energy range of 5.6–17.5 MeV with 9 MeV being found to be the best energy for ⁴⁴Ca irradiations. A simple and fast separation procedure of ⁴⁴Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced ⁴⁴Sc. While ⁴⁴CaCO₃ is relatively expensive, the cost of ⁴⁴Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of ⁴⁴Sc, the availability of ⁴⁴Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging.

It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia in one drug. To achieve this objective, magnetite nanoparticles have been modified in their core with α emitter ²²⁵Ac, in an amount affecting only slightly their magnetic properties. By 3-phosphonopropionic acid (CEPA) linker nanoparticles were conjugated covalently with trastuzumab (Herceptin^®), a monoclonal antibody that recognizes ovarian and breast cancer cells overexpressing the HER2 receptors. The synthesized bioconjugates were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) measurement, thermogravimetric analysis (TGA) and application of ¹³¹I-labeled trastuzumab for quantification of the bound biomolecule. The obtained results show that one ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab bioconjugate contains an average of 8–11 molecules of trastuzumab. The labeled nanoparticles almost quantitatively retain ²²⁵Ac (>98%) in phosphate-buffered saline (PBS) and physiological salt, and more than 90% of ²²¹Fr and ²¹³Bi over 10 days. In human serum after 10 days, the fraction of ²²⁵Ac released from ²²⁵Ac@Fe₃O₄ was still less than 2%, but the retention of ²²¹Fr and ²¹³Bi decreased to 70%. The synthesized ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab bioconjugates have shown a high cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptor in-vitro. The in-vivo studies indicate that this bioconjugate exhibits properties suitable for the treatment of cancer cells by intratumoral or post-resection injection. The intravenous injection of the ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab radiobioconjugate is excluded due to its high accumulation in the liver, lungs and spleen. Additionally, the high value of a specific absorption rate (SAR) allows its use in a new very perspective combination of α radionuclide therapy with magnetic hyperthermia.

The internal α-particle beam of the Warsaw Heavy Ion Cyclotron was used to produce research quantities of the medically interesting Sc radioisotopes from natural Ca and K and isotopically enriched 42Ca targets. The targets were made of metallic calcium, calcium carbonate and potassium chloride. New data on the production yields and impurities generated during the target irradiations are presented for the positron emitters 43Sc, 44gSc and 44mSc. The different paths for the production of the long lived 44mSc/44gSc in vivo generator, proposed by the ARRONAX team, using proton and deuteron beams as well as alpha-particle beams are discussed. Due to the larger angular momentum transfer in the formation of the compound nucleus in the case of the alpha particle induced reactions, the isomeric ratio of 44mSc/44gSc at a bombarding energy of 29MeV is five times larger than previously determined for a deuteron beam and twenty times larger than for proton induced reactions on enriched CaCO3 targets. Therefore, formation of this generator via the alpha-particle route seems a very attractive way to form these isotopes. The experimental data presented here are compared with theoretical predictions made using the EMPIRE evaporation code. Reasonable agreement is generally observed.