Radio-ligand therapy (RLT) with¹⁷⁷Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [¹⁷⁷Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA. The results highlighted some important quality issues of the final preparation: radiolabeling of PSMA-I&T with lutetium-177 needs a considerably longer time compared with the radiolabeling of the well-known [¹⁷⁷Lu]Lu-PSMA-617. When the final product was formulated in saline, the stability of [¹⁷⁷Lu]Lu-PSMA-I&T was reduced by radiolysis, showing a decrease in radiochemical purity (<95% in 24 h). Different formulations of the final product with increasing concentrations of ascorbic acid have been tested to counteract radiolysis and extend stability. A solution of 20 mg/mL of ascorbic acid in saline prevents radiolysis and ensures stability over 30 h.

Computerized decision support systems (CDSSs) are computer programs that provide doctors with person-specific, actionable recommendations, or management options that are intelligently filtered or presented at appropriate times to enhance health care. CDSSs might be integrated with patient electronic health records (EHRs) and evidence-based knowledge. The Computerized DEcision Support in ONCOlogy (ONCO-CODES) trial is a pragmatic, parallel group, randomized controlled study with 1:1 allocation ratio. The trial is designed to evaluate the effectiveness on clinical practice and quality of care of a multi-specialty collection of patient-specific reminders generated by a CDSS in the IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) hospital. We hypothesize that the intervention can increase clinician adherence to guidelines and, eventually, improve the quality of care offered to cancer patients. The primary outcome is the rate at which the issues reported by the reminders are resolved, aggregating specialty and primary care reminders. We will include all the patients admitted to hospital services. All analyses will follow the intention-to-treat principle. The results of our study will contribute to the current understanding of the effectiveness of CDSSs in cancer hospitals, thereby informing healthcare policy about the potential role of CDSS use. Furthermore, the study will inform whether CDSS may facilitate the integration of primary care in cancer settings, known to be usually limited. The increasing use of and familiarity with advanced technology among new generations of physicians may support integrated approaches to be tested in pragmatic studies determining the optimal interface between primary and oncology care. ClinicalTrials.gov, NCT02645357

(1) Purpose: To investigate the role of ⁶⁸Ga-PSMA-11 PET/CT in guiding retreatment stereotactic body radiation therapy (SBRT) in prostate cancer (PCa) patients in biochemical recurrence (BCR) after salvage radiotherapy (S-RT). (2) Methods: We retrospectively evaluated PCa patients previously treated with S-RT on the prostate bed and with proven serum prostate antigen (PSA) failure after S-RT. In all patients (pts), ⁶⁸Ga-PSMA-11 PET/CT was positive in the prostate bed only and guided retreatment SBRT. All retreatments were performed by applying the same radiotherapy protocol (median dose of 18 Gy/3 fractions; IQR 18–21 Gy). The median follow-up was 27 months (range 4–35 months). (3) Results: 38 consecutive patients were considered in this analysis. The overall median PSA level before RT was 1.10 ng/mL (IQR 0.82–2.59). PSA decreased at 3 and 6 months after treatment, with a median value of 0.60 ng/mL (IQR 0.31–0.96; p < 0.001) and 0.51 ng/mL (IQR 0.29–1.17; p < 0.001), respectively. Overall, biochemical recurrence-free survival (b-RFS) was 15.0 months (95% CI 13–23). Grade-1 toxicity was reported in 31.6% of patients (12/38). (4) Conclusion: These results confirm that ⁶⁸Ga-PSMA-11-PET/CT is able to identify the site of recurrence in patients who have failed S-RT, thus supporting the use of metastases-directed radiotherapy as a safe and effective treatment.

This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-223 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Actinium-225 is the most widely studied alpha emitter, with several preclinical and clinical studies on prostate cancer and neuroendocrine tumours. Other types of tumours (such as glioblastoma) still require preclinical and clinical development. Bismuth-213 bound to antibodies, peptides and nanobodies has shown optimal results in preclinical and clinical studies, with increased median survival and no significant toxicity. Astatine-211 differs from most other α-emitters relevant to TAT, since it yields one α-particle per decay. This offers certain translational advantages, including the simplification of radiation dosimetry calculations and quality control (QC). Lead-212 has the advantage of being an in situ generator with likely widespread availability. Although clinical data are limited, the findings are promising at this stage. The unconventional production of Terbium-149 is the primary reason it has not yet progressed to clinical trials. Overcoming this production obstacle would allow more detailed preclinical investigations. Optimal results with Thorium-227-labelled agents have been observed in preclinical studies, including delays in cellular growth, multiple double-strand breaks and complete regression. Intermediate phase I trial results have also been reported, demonstrating safety and tolerability, as well as an objective response rate of 25%.: The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, as well as suggesting that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges.

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [⁶⁸Ga]Ga-PSMA-11 has been the forerunner but a [¹⁸F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental ¹⁸F^-labelled radiopharmaceutical [¹⁸F]F-PSMA-1007 with [¹⁸F]F^- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [¹⁸F]F^- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [¹⁸F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [¹⁸F]F^- from the two suppliers in terms of radionuclidic and radiochemical purity and [¹⁸F]F^- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [¹⁸F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron.