Lutetium [Lu-177] vipivotide tetraxetan 7,400MBq/7.5-12.5ml solution for injection vials

BACKGROUND: Lutetium-177 PSMA radioligand therapy ([¹⁷⁷Lu]Lu-PSMA-RLT) is an effective treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Prospective studies reported favourable efficacy and safety outcomes of up to 6 cycles of [¹⁷⁷Lu]Lu-PSMA. This study aimed to evaluate the efficacy and safety of [¹⁷⁷Lu]Lu-PSMA rechallenge therapy in patients with mCRPC who progressed after an initial course of [¹⁷⁷Lu]Lu-PSMA-RLT. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using relevant keywords in PubMed, EMBASE, and Scopus from establishment to March 2025. Primary endpoints included biochemical responses with a decline in prostate-specific antigen (PSA) of more than 50% and any PSA decline. Secondary outcomes included survival outcomes and treatment-related toxicity following rechallenge therapy with [¹⁷⁷Lu]Lu-PSMA. A random-effects model was used to generate pooled proportions through meta-analysis. RESULTS: Eleven studies with 307 patients were included in the final analysis. Of these, 196 received 177Lu-PSMA RLT alone, and 111 received tandem 177Lu/225Ac-PSMA RLT. The pooled proportions of patients with more than a 50% PSA decline and any PSA decline were 0.45 (95% CI: 0.36–0.54) and 0.71 (95% CI: 0.61–0.80), respectively. In a total of 102 patients, 44 (43%) showed low-grade 1–2 xerostomia; however, no cases of serious xerostomia (grade ≥ 3) were reported. Moreover, the pooled proportion of patients experiencing grade ≥ 3 toxicity was 0.14 (95% CI: 0.09–0.19). CONCLUSION: Rechallenge therapy with [¹⁷⁷Lu]Lu-PSMA is a feasible and safe treatment option for late/end mCRPC patients. Tandem approaches with [225Ac]Ac-PSMA may help expand understanding of how to optimize outcomes after [¹⁷⁷Lu]Lu-PSMA progression. However, these findings require confirmation in prospective, randomized studies comparing different rechallenge strategies to define optimal sequencing and patient selection criteria in advanced prostate cancer.

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BackgroundTargeted radionuclide therapy (TRT) has become a standard of care for patients with metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177 labeled PSMA radioligand therapy ([¹⁷⁷Lu]Lu-PSMA) is an established and effective treatment option, while [²²⁵Ac]Ac-PSMA shows promise in refractory cases. The tandem use of [225Ac] Ac and [177Lu] Lu-labeled PSMA ligands is currently being explored to harness the complementary advantages of both isotopes. This meta-analysis investigates the efficacy and safety of [²²⁵Ac]Ac -/[¹⁷⁷Lu]Lu-PSMA radioligand therapy (RLT) in patients with mCRPC.MethodsThis systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive literature search was performed in PubMed, EMBASE, Web of Science (WOS), and Scopus databases, covering all records from inception through March 2025. The primary endpoints focused on therapeutic efficacy, assessed through PSA-based biochemical responses. These included any PSA decline, a PSA decline of more than 50% from baseline, stable disease (defined as a PSA increase of ResultsEight studies, including a total of 323 patients treated with [²²⁵Ac]-/[¹⁷⁷Lu]-PSMA combination therapy, were analyzed. The pooled response rates showed that 47% (95% CI: 37%-56%) experienced a PSA decline greater than 50%, while 78% (95% CI: 70%-86%) had any measurable PSA decline. The estimated median OS was 11.8 months (95% CI: 9.0-14.6 months). Severe toxicities were infrequent; the most common severe grade ≥ 3 adverse events were anemia (10%) and thrombocytopenia (6%). No cases of grade ≥ 3 xerostomia were reported.Conclusion[²²⁵Ac]Ac-/[¹⁷⁷Lu]Lu-PSMA RLT shows encouraging activity and manageable safety in patients with advanced mCRPC. Given the retrospective nature of the available evidence and limited data, these findings should be further evaluated in prospective trials to determine long-term efficacy and survival outcomes.

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BackgroundDrug interactions with diagnostic radiopharmaceuticals are well recognized, as they can modify biodistribution and lead to false or misleading diagnostic results. However, little is known about such interactions in the field of therapeutic radiopharmaceuticals, despite their rapid expansion-particularly with targeted radionuclide therapies such as Radioligand Therapy (RLT). This review aims, for the first time, to systematically compile and analyze available data on drug interactions involving therapeutic radiopharmaceuticals, in order to support safer and more effective patient care.Main bodyEighty-three articles investigating drug interactions with [177Lu]Lu-oxodotreotide (Lutathera®), [177Lu]Lu-vipivotide tetraxetan (Pluvicto®), [131I]INa, [131I]I-meta-iodobenzylguanidine ([131I]I-MIBG), [223Ra]RaCl2 (Xofigo®), [90Y]Y-ibritumomab tiuxetan (Zevalin®) or [153Sm]Sm-lexidronam pentasodium (Quadramet®) were included. These studies reported 133 drug interactions, 69% of which were not mentioned in the corresponding summaries of product characteristics. Interactions could be beneficial (e.g., reducing renal toxicity) or harmful (e.g., decreasing therapeutic efficacy or potentiating toxicity). Three interactions involved complementary and alternative medicines (quercetin, Ginkgo biloba and ouabain). Overall, the evidence level for reported interactions was low: 88% were classified as level 3 or 4 according to the Centre for Evidence-Based Medicine (CEBM) scale.ConclusionDrug interactions with therapeutic radiopharmaceuticals remain underreported, yet they may have significant clinical consequences. Clinical radiopharmacy plays a key role in detecting and preventing these interactions. Radiopharmacists, through their expertise, can identify potential interactions, influence therapeutic decisions, and positively impact patient management. Their involvement throughout the care pathway is essential to ensure the safe and effective use of these innovative therapies. Nuclear medicine physicians should also be aware that such interactions can alter biodistribution, compromise therapeutic efficacy, and increase the risk of adverse effects.

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BackgroundNuclear medicine procedures are increasingly integrated into routine clinical practice worldwide, including in low- and middle-income settings. Although radiopharmaceuticals have a well-established safety profile, the growing volume of diagnostic and therapeutic procedures means that acute adverse events, while uncommon, are encountered with sufficient frequency to present to emergency departments. Emergency physicians are often the first clinicians to assess patients with post-procedural symptoms, yet guidance tailored to emergency care remains limited. This review aims to provide an emergency medicine-focused synthesis of the incidence, clinical presentation, and acute management of adverse events associated with nuclear medicine procedures.We conducted a narrative review using a systematic search strategy across PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library, covering publications from January 2020 to December 2024. Studies reporting acute events related to radiopharmaceutical administration, including extravasation, allergic reactions, maladministration, and radiation contamination, were included. Evidence from cohort studies, surveillance registries, systematic reviews, and relevant case reports was synthesized narratively due to methodological heterogeneity.Main bodySixty-eight studies encompassing over two million radiopharmaceutical administrations were included. Diagnostic radiopharmaceutical extravasation was common when systematically assessed but rarely resulted in clinically significant harm. Severe allergic reactions and anaphylaxis were exceedingly rare. Maladministration events occurred infrequently and were predominantly associated with diagnostic procedures, with minimal patient harm in most cases. In contrast, extravasation and toxicity related to therapeutic radiopharmaceuticals, particularly high-energy beta emitters, carried greater clinical significance. Newer agents such as lutetium-177-labelled therapies demonstrated predictable toxicity profiles, with hematologic adverse events representing the primary emergency care concern.Emerging alpha-emitting theranostic agents such as actinium-225-PSMA-617 demonstrate promising efficacy but may be associated with clinically relevant xerostomia and hematologic toxicity.ConclusionAcute events related to nuclear medicine procedures are uncommon but clinically relevant in emergency practice. Diagnostic radiopharmaceuticals are generally safe and require supportive management, whereas therapeutic radiopharmaceutical complications warrant heightened vigilance and specialist consultation. Familiarity with these presentations can support timely, appropriate emergency care, particularly in settings with limited on-site nuclear medicine expertise.

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Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

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