To the Editor, prostate cancer (PCa) is the most frequently diagnosed malignancy of the male urinary system globally. With ongoing advancements in clinical treatment paradigms, radionuclide therapy has emerged as a promising novel therapeutic therapy for PCa 1, 2. In recent years, significant advancements in radiopharmaceuticals research for PCa have been driven by substantial investments, technological breakthroughs, and increasing global collaboration 3. Notably, Pluvicto, as the first FDA-approved radiopharmaceutical, achieved annual sales exceeding USD 1 billion in 2024, suggesting that the targeted delivery of radionuclides combined with disease-specific molecules may hold great potential in the PCa therapy. According to this background, we summarized the research status and characteristics of the clinical pipeline for PCa radiopharmaceuticals, hoping to provide potential directions for their research and development (R ARSI, androgen receptor signaling inhibitor; BAT, bipolar androgen therapy; HDACi, histone deacetylase inhibitors; PARPi, poly(ADP-ribose) polymerase inhibitors; PROTAC, Proteolysis-Targeting Chimera; TBK1i, TANK-binding kinase 1 inhibitor. (I) Geographical distribution of clinical trials. Dark blue is indicative of a higher number of studies, while gray is indicative of no studies. (J) Sponsor type classification of clinical trials. As some trials involved multiple funding sources, the total number exceeded 346. (K) Sponsor type distribution for biological-targeted radiopharmaceuticals. (L) Sponsor type distribution for organ-targeted radiopharmaceuticals. Beyond the aforementioned characteristics of radiopharmaceuticals, their global development and accessibility were also influenced by geographic distribution and funding patterns, which may also be crucial for understanding the current landscape and future potential of this field. Therapeutic radiopharmaceuticals possess potential in cancer treatment for its widely acknowledged precision and high efficiency 17. However, widespread adoption is hindered by several challenges, including the limited radionuclide production, R&D constraints, specialized professional training needs, and regulatory framework optimization 18. According to the “Trial Country” field, our analysis of the global distribution of the nuclear drug development pipeline revealed that the United States dominated this field with 150 clinical trials (43.4%), followed by the China (43 trials, 12.4%), Australia (39 trials, 11.3%), United Kingdom (35 trials, 10.1%), and France (34 trials, 9.8%), with remaining trials spreading across other nations (Figure 2I, Supporting Information S1: Table S2). These countries may benefit from the well-established nuclear infrastructures that significantly bolster radiopharmaceutical R&D 19. Conversely, countries in Africa and Asia have lagged behind. Nonetheless, there has been a sharply increasing number of clinical trials (37 trials) in China driven by strategic governmental initiatives “the introduction of the Medium and Long-Term Development Plan for Medical Isotopes (2021–2035)” since 2021, suggesting the pivotal role of policy in radiopharmaceutical advancement. Meanwhile, further investigation based on the “Funding Type” field revealed that academic institutions and enterprises were the most active sponsors of clinical trials, contributing 45.9% and 44.6% of the total funding, respectively, whereas cooperative groups and governments each accounted for 4.6% and 3.0% (Figure 2J). Moreover, a detailed analysis of the funding distribution revealed that industry funding tends to favor RDC development (48.5%), whereas academia allocates more resources toward organ-targeted approaches (49.6%) (Figure 2K,L). Collectively, substantial funding provided by industries and academia may largely provide support for the R&D, practical application, and commercial value transformation of radiopharmaceuticals in the future. In conclusion, radiopharmaceutical therapy is a rapidly evolving and promising strategy for the PCa treatment. Based on the analysis of global clinical trial registry data, we observed a steady increase of trial number, with a clear shift toward biologically targeted RDCs. Most trials remained in early phases, and radionuclide types continued to be diverse, though therapeutic targets were still dominated by PSMA, highlighting the need for expanded target discovery to support more precise clinical applications. β emitting radionuclides are prevalent in current trials, whereas α emitting agents may be a potential next generation direction for theoretical advantages in tumor selectivity and thus warrant further investigation. Indications for radiopharmaceuticals are gradually expanding beyond mCRPC to include other disease states, yet most of these efforts are still in early clinical stages and require additional evidence to confirm clinical value. Combination strategies are increasingly adopted, which may aim to enhance treatment effects and address tumor heterogeneity. However, detailed clinical benefits remain to be validated. Geographically, clinical development is concentrated in a small number of countries with established nuclear medicine infrastructure, whereas China has shown rapid growth driven by national policy support. Academic institutions and industry are the primary funding sources, with distinct investment preferences between RDCs and organ targeted agents. Collectively, though substantial progress has been made in the clinical development of PCa radiopharmaceuticals, the field remains in an early phase of clinical translation. Continued improvements in radionuclide production, research infrastructure, and regulatory coordination may facilitate the widespread implementation of PCa radiopharmaceuticals. Furthermore, strengthening collaboration among academia, industry, and regulatory agencies may also be beneficial for accelerating innovation, optimizing the R&D of radiopharmaceuticals, and promoting their widespread application in clinical practice. This study was supported by the National Natural Science Foundation of China (Grant Nos. 82273373, 82573849), Yunnan Natural Science Foundation (Grant Nos. 202401AS070019, 202201AY070001-045), 535 Talent Project of First Affiliated Hospital of Kunming Medical University (Grant No. 2023535D15), and Yunnan Health Training Project of High-Level Talents (Grant No. D-2024028). The authors declare no conflicts of interest. Trialtrove database is a commercial, curated clinical intelligence platform rather than a public primary clinical trial registry. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dong et al. (Wed,) studied this question.