Irene Marini

Background/Objectives: Vacuum-assisted breast biopsy (VABB) is widely used for the diagnosis of nonpalpable breast cancer but is not considered definitive treatment because microscopic residual disease may persist within or around the biopsy cavity. The ARTHE phase I trial evaluated a cavity-targeted radionuclide strategy based on same-session sequential intralesional administration of avidin followed by [⁹⁰Y]Y-DOTA-biotin after VABB. Methods: Eighteen women with nonpalpable breast cancer measuring ≤15 mm and a skin-to-cavity distance ≥ 13 mm were treated in three sequential activity-escalation cohorts. The primary objective was to assess acute local and systemic safety, including dose-limiting toxicity. The protocol-specified co-primary objective was to evaluate preliminary antitumor activity, assessed as breast-only pathologic complete response (pCR) at surgery. Given the phase I single-arm design, pCR was analyzed descriptively. The protocol-specified secondary objective was patient-specific dosimetry. Additional exploratory assessments included post-injection biodistribution and integration with subsequent breast-conserving surgery. Results: No dose-limiting toxicities, grade ≥ 3 adverse events, clinically relevant hematologic toxicity, treatment discontinuations, hospitalizations, or treatment-related surgical delays were observed. Local toxicity was limited to grade 1 injection-site pain and/or erythema. Post-injection imaging consistently demonstrated focal intralesional localization without clinically relevant extra-lesional uptake. All patients underwent breast-conserving surgery 4–7 weeks after treatment. No residual tumor cellularity (RTC), from either invasive or in situ carcinoma, was identified in the breast surgical specimen in 5/18 patients (27.8%). However, because diagnostic VABB may have removed part or all of the malignant lesion, the absence of residual carcinoma at surgery cannot be attributed specifically to the radionuclide treatment. Conclusions: The intralesional avidin-mediated local trapping strategy using [⁹⁰Y]Y-DOTA-biotin after VABB was feasible, showed favorable acute and short-term tolerability, was associated with early focal localization on post-injection imaging, and was compatible with standard breast-conserving surgery. Controlled studies are warranted to determine the therapeutic contribution of this post-biopsy cavity-targeted strategy, optimize administered activity, and refine patient selection.

The widespread adoption of prostate-specific membrane antigen (PSMA)-targeted PET/CT has profoundly reshaped molecular imaging in prostate cancer and has substantially reduced the routine use of radiolabeled choline tracers. However, the transition from choline to PSMA imaging should not be interpreted simply as the replacement of one radiopharmaceutical by another, but rather as part of a broader evolution from metabolism-based imaging toward receptor-targeted and biology-driven imaging strategies. This narrative review critically reassesses the residual and emerging role of choline PET/CT in the PSMA era, with particular attention to the biological rationale of choline uptake, selected prostate cancer scenarios, and extra-prostatic applications. In prostate cancer, PSMA PET/CT remains the dominant imaging modality because of its superior diagnostic performance, particularly in biochemical recurrence; nevertheless, choline PET/CT may provide complementary metabolic information in highly selected settings, including PSMA-low or heterogeneous disease, aggressive or dedifferentiated variants, neuroendocrine transformation, equivocal PSMA findings, and limited PSMA availability. These prostate cancer applications, however, are supported mainly by biological rationale, indirect evidence, and limited clinical data and should therefore be regarded as exploratory rather than established indications. By contrast, ¹⁸F-fluorocholine PET/CT has emerged as a clinically established imaging modality in primary hyperparathyroidism, particularly after negative or inconclusive conventional imaging, with prospective studies and meta-analyses demonstrating high detection rates and superior performance compared with conventional scintigraphic techniques. Additional applications in hepatocellular carcinoma and selected neuro-oncologic settings remain exploratory and require further validation. Overall, choline PET/CT should not be considered obsolete in the PSMA era, but selectively repositioned within biology-driven and multiparametric imaging strategies, with its strongest evidence currently supporting primary hyperparathyroidism and its other applications requiring cautious interpretation and further prospective validation.

Background: Radiometabolic ¹⁷⁷ Lu-based treatment is a process that involves different specialists. Due to its high complexity and to the potential serious risk of health damages for patients and healthcare professionals, a global analysis of the whole process would allow to identify the weak points and then to improve clinical standards. Radioprotection risk assessment also fulfils the requirement of the 2013/59/EURATOM directive. Aim: To identify the main critical points in the process of ¹⁷⁷ Lu therapies by using the failure mode and effects analysis (FMEA) method. The focus of the FMEA analysis is the risk to the patient. Materials and methods: We divided the whole process of ¹⁷⁷ Lu-based therapies into main steps and identified all possible failure modes. Each failure mode was scored for severity (S), occurrence (O) and detectability (D), range 1–10. Based on the Risk Priority Number (RPN = SxOxD), all failures were ranked. Both in-house labelled or already and ready-for-injection radiopharmaceuticals were considered, as well as both ¹⁷⁷ Lu-PSMA and ¹⁷⁷ Lu-DOTATATE/TOC therapies. Results: The failure modes with the highest RPN scores identified were: incorrect infusion supervision based on count measurements, incorrect catheter connections (vial–injection pump–patient), incorrect end of infusion, and false-negative pregnancy test results. Additionally, for in-house labelled radiopharmaceuticals, the incorrect selection of calibration factors in the activimetre for vial activity measure was identified as a critical issue. Conclusions: The FMEA analysis allowed the identification of the main failure mode in ¹⁷⁷ Lu treatment procedures. Based on the obtained results, strategies could be implemented in clinical practice in order to further improve patient safety. The present results may help the new implementation of ¹⁷⁷ Lu-based therapy in the perspective of increasing use of these therapies.

Introduction: There is a critical need for innovative therapies beyond the current standard of care for meningiomas and gliomas. Radioligand therapy (RLT), with its theranostic approach, holds significant promise in this regard. Although several reviews on this topic have been published, none yet have combined the utilization of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology with the Critical Appraisal Skills Programme (CASP) analysis, along with a dedicated subsection specifically addressing ongoing and completed clinical trials. This review aims to fill this gap in the literature by providing a comprehensive assessment of the current evidence on RLT in these tumors. Materials and methods: Published studies were searched through PubMed, Scopus, and Web of Science up to 30 April 2025. Only original articles and clinical studies were included. Following a structured selection process, data extraction was performed. Study quality was critically appraised using CASP analyses. For clinical trials, an additional search was conducted on ClinicalTrials.gov beginning on 12 May 2025. Results: A total of 30 studies were included in the review: 22 on meningiomas (290 patients) and 8 on gliomas (259 patients). For each study, first author, journal, year of publication, somatostatin receptor imaging, study design, radiopharmaceutical used, main topics, response criteria, toxicity assessment, post-therapy scintigraphy, number of patients, WHO grade, demographics, findings and median follow-up were considered. Among clinical trials, 22 were analyzed, including study site, year of first submission, proposed radiopharmaceutical, study type, primary endpoints and status. Efficacy and toxicity data were the primary focus, and the findings were generally encouraging. Studies on RLT in meningiomas was more robust, while in gliomas remained largely experimental. Nevertheless, the authors’ critical appraisal was generally positive. Clinical trials confirmed the more “traditional” nature of research in meningiomas compared to gliomas. Conclusion: Despite the heterogeneity of the studies, RLT emerges as a promising therapeutic strategy in neuro-oncology. Its theranostic paradigm offers a distinctive advantage, enabling patient selection, treatment personalization, and response monitoring. The development of potentially novel radiopharmaceuticals and the conduct of well-designed multicenter trials with standardized response criteria are needed to further increase the impact and clinical translation of RLT in neuro-oncology.

Purpose Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge. Radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA-617 has shown promising efficacy. This study reports the first Italian prospective trial evaluating efficacy and safety at 5.5 GBq per cycle in mCRPC. Methods This prospective, single arm, monocentre, Phase-II study enrolled PSMA-avid mCRPC patients (April 2017–October 2022). Patients received 5.5 GBq of ¹⁷⁷Lu-PSMA-617 per cycle for four cycles at 8 ± 2 weeks; up to two additional cycles were allowed. Mannitol and polyglutamate tablets were given to limit renal and salivary uptake. Primary endpoint was PSA response, assessed as best response; secondary endpoints were safety, progression-free survival (PFS) according to PCWG3 criteria, and overall survival (OS). Adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results Forty-eight patients were assessed for safety; 44 were evaluable for efficacy. A ≥ 50% PSA decline occurred in 22 patients (50%). At 12 months, PFS was 22.7% (95% CI: 11.8–35.9) and OS 87.9% (95% CI: 73.4–94.8); median OS was 18.8 months. Treatment was generally well tolerated, with mostly Grade 1–2 events. Grade 3 toxicities were rare (6.3%), and no Grade 4 events occurred. One Grade 3 hyponatraemia led to discontinuation. Conclusions ¹⁷⁷Lu-PSMA-617 at 5.5 GBq per cycle was safe and effective, achieving survival comparable to studies using 7.4 GBq with fewer severe toxicities. Tailored regimens may benefit patients at higher toxicity risk. These data support further studies to optimize dosage, timing, sequencing and combinations of RLT.