the Quarterly Journal of Nuclear Medicine and Molecular Imaging最新文献

Prostate-specific membrane antigen-targeted radioligand therapy (PSMA RLT) has recently emerged as a promising treatment for patients with metastatic prostate cancer. Building on the success of PSMA PET diagnostics, PSMA RLT has attracted interest from both research institutions and pharmaceutical companies, leading to a progressive increase in clinical trials over the past decade. In 2022, the first PSMA RLT agent, [¹⁷⁷Lu]Lu-PSMA-617, was approved by the FDA and EMA for the treatment of mCRPC patients progressing after standard therapies. Since then, the number of centers offering PSMA RLT has grown rapidly worldwide. In March 2025, the FDA expanded the indication for [¹⁷⁷Lu]Lu-PSMA-617 to include taxane chemotherapy-naïve mCRPC patients. Current research studies are focusing on expanding the indications for PSMA RLT, developing new PSMA-targeting agents, exploring alternative radionuclides such as alpha and Auger electron emitters, and investigating combination strategies. Despite these advancements, several significant challenges remain in clinical implementation, global access, and availability. To present, there is high variability among different countries and institutions in patient selection and treatment protocols. Moreover, the distribution of centers offering the treatment is highly heterogeneous, with significant disparities across different countries. Furthermore, workforce shortages are already hindering its widespread diffusion and are expected to limit its expansion, particularly in low and middle-income countries. Many barriers need to be overcome in the coming years to standardize treatment protocols, guarantee fair global access to the treatment, and achieve widespread accessibility. Addressing these challenges is crucial to maximize the potential of PSMA RLT as a leading treatment for prostate cancer.

With the growth and surge of prostate cancer theranostics globally, multiple targeted radionuclide therapy (TRT) agents have been utilized to aim to provide a tumoricidal effect to patients who would benefit from TRT. Despite the fact that approved isotopes such as Strontium-89, Samarium-153 and Radium-223 exist, Lutetium-177 prostate specific membrane antigen (PSMA) has revolutionized the impact of radioligand therapy (RLT) in this domain. Key defining clinical trials such as the VISION, TheraP and PSMAfore trials have given clear evidence of the benefit of PSMA RLT in the treatment landscape of metastatic castrate resistant prostate cancer. A number of other radioisotopes in the PSMA RLT domain have also more recently come into the field, notably Terbium-161, Copper- 67 and Iodine-131. Targeted Alpha Therapy (TAT) has grown significantly as well over the last few years owing to physical properties of its high linear energy transfer and DNA damage provided by alpha particles in comparison to beta particles. Actinium-225 PSMA based TAT has formed the basis of prostate cancer theranostics since its initial application, however, many other alpha isotopes are being explored owing to some of the side effects that Actinium-225 presents. Astatine-211, owing to its shorter half-life, has become a more attractive option for its potential utilization in prostate cancer theranostics. Whilst there is preclinical work detailing its efficacy in suppressing tumor growth and limited toxicity profiles, translation into humans is still in its infancy and requires further exploration. A number of clinical trials have utilized Astatine-211 in other malignancies with virtually no work related to prostate cancer. Moreover, the logistics and infrastructure required to support global efforts to make Astatine-211 more readily available should be high on the agenda as well. This narrative review of the literature aims to showcase the current status of Astatine-211 efforts in prostate cancer care with available data (including clinical trials).

Metastatic castration-resistant prostate cancer (mCRPC) is an unavoidable advanced condition associated with short-term survival and poor prognosis. It is a heterogeneous disease, difficult to monitor based only on serum PSA levels. For this reason, systematic use of PSMA PET-based response criteria should be considered to assess therapy efficacy in mCRPC to improve treatment decision-making, patients' outcomes, and cost-effectiveness. Our review focuses on most common morphologic and metabolic response criteria and their application for the detection and therapy response assessment of PC patients, particularly in the setting of mCRPC, highlighting relative strengths and weaknesses, as well as potential future applications in the era of RLT.

Introduction: Neuroendocrine prostate cancer (NEPC) is a rare cancer subtype with significant prognostic implications. This systematic review aims to explore the current landscape of positron emission tomography (PET) imaging and radionuclide therapy in this rare entity.

Evidence acquisition: The Scopus and PubMed online databases were systemically reviewed to identify relevant studies on the topic of interest.

Evidence synthesis: A total of 60 studies reporting such evidence in 102 patients were retrieved. A total of 179 PET/CT examinations were performed across all NEPC patients, with [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) being the most frequently utilized radiotracer (45% of NEPC patients), followed by [⁶⁸Ga]Ga-DOTA-peptides (22%), [⁶⁸Ga]Ga-prostate specific membrane antigen ([⁶⁸Ga]Ga-PSMA) (18%), and other PET tracers (15%). Single-modality PET/CT imaging was mostly employed to evaluate NEPC extent, detect unusual metastatic sites, assess therapy response, and guide for biopsy sites in cases of hormone-secreting NEPC. Multimodal PET/CT utilizing dual- or triple-tracer approaches was employed for collective NEPC interpretation, assessment of heterogeneity, therapy response assessment, and determination of radionuclide therapy eligibly. For treatment, 16 [¹⁷⁷Lu]Lu-DOTATATE cycles, administered to 7 patients, produced effective disease control in all patients. One patient received both [¹⁷⁷Lu]Lu-PSMA and [¹⁷⁷Lu]Lu-DOTATATE, achieving partial response, while another patient receiving 4 [¹⁷⁷Lu]Lu-PSMA cycles also showed a partial response.

Conclusions: The multimodal molecular imaging approach appears to be the most effective for NEPC evaluation and determination of radionuclide therapy eligibility. [¹⁷⁷Lu]Lu-based therapies seem to be a compelling treatment approach to be pursued in eligible cases, although larger studies are needed to confirm the current findings.

Background: This study aims to further strengthen the evidence of tumor sink effect (TSE) and to confirm this phenomenon in patients undergoing ²²⁵Ac/¹⁷⁷Lu-PSMA tandem radioligand therapy.

Methods: The study included a total of N.=31 mCRPC patients who undergone two cycles of [¹⁷⁷Lu]Lu-PSMA-617 RLT, with at least one cycle being augmented by [²²⁵Ac]Ac-PSMA-617. For pre- and post-therapeutic [⁶⁸Ga]Ga-PSMA-11 PET/CT scans the standardized uptake value (SUVmean) of the liver, kidneys, parotid glands, and spleen as well as the total lesion PSMA (TLP) were assessed and compared.

Results: The mean TLP value decreased by 31.32% after two cycles of PSMA-RLT. Overall, significant increases in SUVmean were noted in the spleen (P=0.002) and liver (P=0.009). Especially, responders exhibited significant SUVmean increases in the spleen (P<0.001, baseline mean: 5.35 vs. follow-up mean: 7.28), liver (P=0.001, 4.21 vs. 5.00), and kidney (P=0.003, 17.30 vs. 20.43). Correlation analysis revealed significant relationships between change in TLP and change in SUVmean in the parotid gland (r=0.408, P=0.023) and spleen (r=0.410, P=0.022). The strength of TSE varied with tumor size, with an increase in tumor burden leading to a stronger TSE.

Conclusions: This analysis demonstrates the presence of the TSE in mCRPC patients undergoing the innovative ²²⁵Ac/¹⁷⁷Lu-PSMA tandem radioligand therapy concept. TSE may hold significant clinical implications and may play a role towards more individualized RLT.

Prostate cancer (PCa) is a heterogeneous disease and prevalent malignancy in men, necessitating accurate imaging techniques to facilitate effective diagnosis and management. Recent evidence has demonstrated that [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) and prostate-specific membrane antigen (PSMA)-targeted PET tracers positron emission tomography/computed tomography (PET/CT) imaging can provide complementary biological information, thereby improving diagnostic accuracy and the assessment of lesion heterogeneity in patients with PCa. However, optimal protocols for PSMA/FDG dual-tracer PET/CT and PET/magnetic resonance (PET/MR) imaging remain under investigation. Total-body PET/CT, with its enhanced sensitivity, enables imaging with low tracer activity and facilitates the development of novel dual-tracer PET/CT imaging protocols. PET/MR offers additional valuable information for the diagnosis and local staging of PCa due to its superior soft tissue resolution and multiparametric capabilities. Thanks to the longer MR acquisition time, it is possible to perform low-activity radiotracer PET imaging with the same long-time MR acquisition. Additionally, advancements in time-of-flight technology and the improved sensitivity of PET systems further make low-activity radiotracer PET/MR imaging clinically feasible. Given that expertise in total-body PET/CT imaging technology and access to PET/MR scanners are limited to a relatively small number of institutions worldwide, this review provides clinical exploration to optimize workflows for [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]FDG dual-tracer PET/CT and PET/MR imaging, with a focus on radiation dose reduction through dual-low-activity-tracer imaging protocols.

Radiopharmaceutical therapy is emerging rapidly as an effective and safe pillar in cancer management. The regulatory approvals for ¹⁷⁷Lu-PSMA-617 radiopharmaceutical therapy in both the pre- and post-chemotherapy metastatic castration resistant prostate cancer clinical space have paved the way for the implementation of this life-prolonging therapy in clinical practice. However, the emergence of resistance to radiopharmaceutical therapy is inevitable, and therefore, combination therapies will be needed to synergize treatment efficacy without untoward collective toxicity. Biologically rational combination therapies across various phases of prostate cancer will lead to more optimal patient outcomes than what can be achieved with monotherapy. This article summarizes select clinical trials on prostate-specific membrane antigen-targeted radiopharmaceutical therapy in combination with other treatments that are either actively accruing or have provided preliminary results.

Targeted alpha therapy (TAT) has shown promise in prostate cancer patients, both hormone-sensitive and castration-resistant, with or without prior treatment. TAT's radiobiological properties explain why it is more potent than other forms of ionizing radiation, such as the clinically approved [¹⁷⁷Lu]Lu-PSMA-617. Although most TAT agents used in compassionate care or clinical trials target the prostate-specific membrane antigen (PSMA), some alternatives are yet to be used clinically, some of which aim to address PSMA-negative prostate cancer. These include [²²³Ra]RaCl2, which is approved for palliative bone pain, and a variety of other non-PSMA antigen or receptor-targeting medicines. Whereas this study focuses on TAT medicines that are currently available for clinical use, it also explores these preclinical agents.

Introduction: This systematic review investigates the potential of artificial intelligence (AI) in improving the accuracy and efficiency of prostate-specific membrane antigen positron emission tomography (PSMA PET) scans for detecting metastatic prostate cancer.

Evidence acquisition: A comprehensive literature search was conducted across Medline, Embase, and Web of Science, adhering to PRISMA guidelines. Key search terms included "artificial intelligence," "machine learning," "deep learning," "prostate cancer," and "PSMA PET." The PICO framework guided the selection of studies focusing on AI's application in evaluating PSMA PET scans for staging lymph node and distant metastasis in prostate cancer patients. Inclusion criteria prioritized original English-language articles published up to October 2024, excluding studies using non-PSMA radiotracers, those analyzing only the CT component of PSMA PET-CT, studies focusing solely on intra-prostatic lesions, and non-original research articles.

Evidence synthesis: The review included 22 studies, with a mix of prospective and retrospective designs. AI algorithms employed included machine learning (ML), deep learning (DL), and convolutional neural networks (CNNs). The studies explored various applications of AI, including improving diagnostic accuracy, sensitivity, differentiation from benign lesions, standardization of reporting, and predicting treatment response. Results showed high sensitivity (62% to 97%) and accuracy (AUC up to 98%) in detecting metastatic disease, but also significant variability in positive predictive value (39.2% to 66.8%).

Conclusions: AI demonstrates significant promise in enhancing PSMA PET scan analysis for metastatic prostate cancer, offering improved efficiency and potentially better diagnostic accuracy. However, the variability in performance and the "black box" nature of some algorithms highlight the need for larger prospective studies, improved model interpretability, and the continued involvement of experienced nuclear medicine physicians in interpreting AI-assisted results. AI should be considered a valuable adjunct, not a replacement, for expert clinical judgment.