Lu-177 PSMA-617 / PSMA-I&T evidence — VISION, PSMAfore, dosimetry, salivary-gland and kidney safety. Curated daily from Europe PMC (PubMed + PMC + preprints) and OpenAlex — free-full-text link on each open-access paper.
Jialiang Deng, Guoxiong Ma, Weijin Chen, Songhao Wen et al.
[ 177 Lu]Lu-PSMA radioligand therapy (LuPSMA RLT) has improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), yet clinically meaningful response heterogeneity persists even among patients selected on the basis of PSMA PET positivity. A central limitation of patient-level PSMA eligibility is that it establishes target availability in at least…
Longitudinal oncologic imaging poses a tracking challenge because lesions can split, merge, or transiently disappear, violating one-to-one correspondence assumptions. We propose spatio-temporal lesion graphs constructed via nearest-centroid matching across all previous time points for lineage assignment, with bidirectional matching between consecutive scans to classify splits, …
Introduction The notion of microtubule (MT) dynamics relates to the changes in the length of MT polymers in living cells. They are governed by a stochastic process related to the rates and chances of adding or removing tubulin dimers at the ends of MT polymers, termed dynamic instability. The ability of each MT to swiftly switch between stages of adding or removing dimers at th…
Robert N Spaans, Nadieh Khalili, Geert Litjens, Jean‐Paul A. van Basten
Samenvatting De stijgende incidentie van prostaatkanker en toenemende zorgdruk vragen om efficiëntere, gepersonaliseerde zorg. Binnen de primaire diagnostiek ondersteunen CE-gecertificeerde systemen PI-RADS-analyse en Gleason-predictie. Tijdens stadiëring kan AI ingezet worden voor detectie en kwantificering van PSMA-positieve laesies op PSMA-PET/CT en metastasedetectie op CT e…
Lutetium-177 (Lu-177) is widely used in radionuclide therapy, where accurate activity measurement prior to administration is essential for safe and effective treatment delivery. However, variability in dose calibrator response due to measurement conditions and source geometry remains a practical challenge in routine clinical settings. This study presents a practical clinical ca…
Matthew Benger, Georgios Krokos, Karan Daga, Alan J. Wright et al.
Abstract Prostate-specific membrane antigen (PSMA) is upregulated in high-grade glioma (HGG). This study aimed, firstly, to establish dosimetry for the radionuclide [68Ga]-PSMA-11 in HGG patients; secondly, to determine theoretical tumour doses for [177Lu]-PSMA, a potential therapeutic radionuclide; thirdly, to assess PSMA immunohistochemistry in targeted intra-operative HGG bi…
The application of artificial intelligence (AI) in positron emission tomography (PET)-based internal dosimetry in radiopharmaceutical therapy (RPT), with an emphasis on the paradigm shift from resource-consuming multi-time-point acquisition protocols toward efficient data-driven dosimetric frameworks. Machine learning (ML) models capable of determining organ- and patient-specif…
Luca Russo, Ossian Longoria, Silvia Bottazzi, Nuria Porta et al.
Background Unequivocal clinical progression without radiological progression according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria is recognised in metastatic castration-resistant prostate cancer (mCRPC), reflecting limitations of bone scintigraphy in distinguishing an osteoblastic progression from an osteoblastic flare. Objective To compare the METastas…
Stephanie Robinson, Elizabeth Morris, Sofia Michopoulou, Richard Boardman et al.
OBJECTIVE: Bone marrow cellularity is routinely estimated from a small number of 2D histology sections, making assessment sensitive to section representativeness, processing artefacts and observer interpretation. Three-dimensional X-ray histology (XRH), using computed microtomography (µCT), enables non-destructive whole-block imaging of trephine biopsies. This study evaluated w…
Leonardo Lampertico, Gaia Muti, C. Carbonini, Chiara Romanò et al.
The accuracy of quantitative lutetium-177 single-photon emission computed tomography/computed tomography (¹⁷⁷Lu SPECT/CT) depends on the imaging system, acquisition protocol, reconstruction algorithm, and calibration strategy. This study aimed to develop and evaluate a practical commissioning workflow to optimize ¹⁷⁷Lu imaging across different commercial scanner–reconstruction …
Cerci JJ, Fanti S, Herrmann K, Rodrigues DF et al.
Real-world disparities in access to PSMA-targeted theranostics are poorly characterized. We compared waiting times for PSMA PET/CT and 177Lu-PSMA therapy between centers in Brazil and Europe. Methods: This retrospective multicenter study included 91 patients (50 from Brazil, 41 from Europe) treated with 177Lu-PSMA. Outcomes were days from request to PSMA PET/CT completion (diag…
Christopher Montemagno, Benjamín Serrano, Benoît Paulmier
Theranostics occupies a unique position in oncology because the same molecular target simultaneously enables disease visualization and therapeutic delivery. Unlike most anticancer strategies, where biomarkers primarily determine treatment eligibility, theranostic targets directly connect molecular imaging with targeted radionuclide therapy, making them the biological foundation…
Hao Zhang, Yekuan Shi, Yanqin Yu, Zongxi He et al.
Abstract Objective Metastatic castration-resistant prostate cancer (mCRPC) remains associated with poor long-term outcomes, and survival under current treatment is modest. Prostate-specific membrane antigen (PSMA)-targeted alpha therapy using 225 Ac exhibits superior cytotoxicity compared with beta-emitting radiopharmaceuticals; however, dose-limiting xerostomia from salivary g…
E Novruzov, Eduards Mamlins, Joseph Kabunda, Jens Cardinale et al.
Abstract Background PSMA-PET/CT became an important means for prostate cancer management. The high-resolution and signal-to-noise ratio of PET is mandatory in primary staging or biochemical relapse that often present with tiny lesions. PSMA-PET is also used to select patients for PSMA-targeted radioligand-therapy, but scanner availability increasingly becomes a bottleneck. The …
Aramis Raiola, Fabio Acerbi, Cyril Martin Alispach, Domenico della Volpe et al.
Abstract Background The POSiCS camera is a handheld and wireless, small field-of-view gamma camera developed for use in radio-guided surgery (RGS), with sentinel lymph node biopsy (SLNB) as its benchmark application. This compact and lightweight detector (about $$350\,\textrm{g}$$ ) maps tissues labeled with a $${^{99m}\hbox {Tc}}$$ radiotracer to highlight target lesions. By e…
[177Lu]Lu-PSMA-617 improves survival and quality of life in men with metastatic castration-resistant prostate cancer but requires substantial healthcare involvement. Our analysis evaluated the time toxicity associated with [177Lu]Lu-PSMA-617, representing the first dedicated radioligand time toxicity assessment. We conducted a multi-institutional retrospective study of patients…
Adrien Holzgreve, Sophie C. Siegmund, Liam Widjaja, Rudolf A. Werner
management of patients with advanced prostate cancer, firmly anchored in clinical guidelines [8].This article provides an update on established PSMA theranostics using beta-emitting ligands, based on major clinical trial results.It then continues with an overview of more recent developments in the field of PSMA radiotheranostics, focusing on alpha-based approaches, in particula…
PurposeThe successful preclinical efficacy studies prompted a Phase I clinical trial to investigate [161Tb]Tb-SibuDAB. Deeper insight into potential undesired effects on normal tissues and organs remained to be investigated. The aim of this preclinical study was, therefore, to assess and compare the tolerability of [161Tb]Tb-SibuDAB with that of [177Lu]Lu-SibuDAB, [161Tb]Tb-PSM…
Bekkhoucha A, Zaragori T, Olivier P, Claudin M et al.
Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy with [177Lu]Lu-PSMA-617 has reshaped the management of metastatic castration-resistant prostate cancer (mCRPC). This study aimed to assess the added prognostic value of [18F]FDG PET beyond [68Ga]Ga-PSMA-11 PET as pretreatment imaging and to develop an overall survival (OS) nomogram for patients with …
[177Lu]Lu-PSMA-617 is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC); however, response rates vary significantly, particularly among patients with low prostate-specific membrane antigen (PSMA) expression on PSMA PET. This multicenter, open-label phase 2 trial evaluates the efficacy and safety of an intensified Lu-PSMA treatment schedule in patie…
Park HL, Kersting D, Bergstrom CP, Khaki AR et al.
This article evaluates whether early same-day posttherapy whole-body SPECT/CT assessed using visual RECIP 1.0 is associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) that is positive for prostate-specific membrane antigen (PSMA) and treated with [177Lu]Lu-PSMA-617, and it assesses concordance among posttherapy SPECT/CT, …
Background and objectiveLutetium-177-PSMA radioligand therapy ([177Lu] Lu-PSMA) is an emerging targeted treatment for metastatic castration-resistant prostate cancer (mCRPC). We evaluated the comparative efficacy, safety, and quality-of-life (QoL) impact of [177Lu] Lu-PSMA versus contemporary standard-of-care (SOC) regimens in mCRPC.MethodsWe conducted a systematic review and m…
The TheraP trial compared cabazitaxel to Lutetium-177-labeled PSMA-617 (Lu-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) following docetaxel and an androgen receptor pathway inhibitor (ARPI). Lu-PSMA demonstrated improved PSA response (66% vs 37%; p < 0.0001) and progression-free survival (HR = 0.63; p = 0.0028), while overall survival (OS; median 16.4 vs. 19…
A contemporary standard of care for patients with metastatic androgen pathway modulator-naive/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) until progression. PSMAddition aimed to evaluate the efficacy and safety of [177Lu]Lu-PSMA-617 (177Lu…
Schwengber WK, Sanders J, Pinteric A, Armitage L et al.
Radiopharmaceutical therapy (RPT) uses radionuclides linked to targeting ligands to bind tumor-associated receptors or antigens and deliver ionizing radiation to malignant cells. Approved agents include [177Lu]Lu-DOTATATE for gastroenteropancreatic neuroendocrine tumors, [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer, and 223Ra-dichloride for bone-predom…
Metastatic castration-resistant prostate cancer (mCRPC) remains challenging to treat, especially after failure of standard therapies, such as androgen receptor pathway inhibitors and taxane-based chemotherapy. Radiopharmaceutical therapy with [177Lu]Lu-PSMA-617 targets prostate-specific membrane antigen (PSMA)-positive tumor cells. In the VISION trial, [177Lu]Lu-PSMA-617 has de…
Kwon JY, Cheville JC, Muniz-Rincon M, Ahmed ME et al.
Pleomorphic giant cell carcinoma (PGCC) of the prostate is an extremely rare and aggressive malignancy with limited treatment options. We present a case report of metastatic PGCC patients treated with 177Lu-PSMA-617 radioligand therapy (Pluvicto) after progression on standard therapies. Both patients had PSMA-avid tumors on imaging. Molecular profiling revealed mutations in hal…
Over a period of 10 y, our center treated 766 patients with prostate cancer using 177Lu-PSMA (177Lu-PSMA-617 or 177Lu-PSMA I&T). We report 5 cases of 177Lu-PSMA-induced thrombotic microangiopathy (TMA). Methods: In this retrospective analysis, we reviewed data from all patients at our center who developed histologically confirmed renal TMA after 177Lu-PSMA. Clinical, biochemica…
Targeted radionuclide therapy (TRT) with 177Lu holds a huge clinical success in treating advanced prostate cancer patients. It is noted, however, that 177Lu with moderate radiation energy achieves effective tumor inhibition at a relatively high dose and has a low capacity to activate "cold" prostate tumor. In this study, we report that Sigma-1 receptor and prostate-specific mem…
OPTIMAL-PSMA aims to determine the safety and efficacy of a dose-intensified (intense induction followed by a maintenance period) regimen of [177Lu]Lu-PSMA-597 compared with the standard-of-care regimen (every 6 wk for up to 6 doses) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: OPTIMAL-PSMA is a phase 2, open-label, 2-arm, multicenter, rand…
This is a dosimetry analysis of the prospective randomized phase 2 trial RESIST-PC which evaluated the efficacy and safety of 2 injected activity regimens of [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer. Methods: This biinstitutional study randomized patients with metastatic castration-resistant prostate cancer to receive eithe…
ObjectiveTo identify independent prognostic factors in castration-resistant prostate cancer (CRPC) patients with visceral metastases, construct and internally validate a prognostic nomogram for individualized risk stratification, and generate a hypothesis-driven framework that may inform future candidate selection for radionuclide therapies-including lutetium-177 PSMA-617 (177L…
Objective¹⁷⁷Lu is an approved radionuclide for targeted radionuclide therapy (TRT), first established with ¹⁷⁷Lu-DOTATATE for neuroendocrine tumors, and subsequently with PSMA-targeted therapy. The widespread adoption of these therapies is expected to substantially increase radioactive waste generation. The long-lived isomer ¹⁷⁷ᵐLu, present as an impurity in ¹⁷⁷Lu preparations,…
BackgroundRadioligand therapy targeting the prostate-specific membrane antigen (PSMA) has been established as a key treatment for PSMA-positive metastatic castration-resistant prostate cancer following the approval of [177Lu]Lu-PSMA-617 (177Lu). However, variable responses, resistance, uncertain treatment sequencing, and limited efficacy in selected biological settings remain m…
ObjectiveProstate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) provides a survival advantage in metastatic castration-resistant prostate cancer (mCRPC). However, the physiologically high PSMA-ligand uptake in salivary glands makes these organs susceptible to radiation damage. The aim of this study is to examine the changes occurring in salivary glands aft…
Agrawal R, Parghane RV, Joshi A, Prabhash K et al.
IntroductionA subset of prostate cancer progresses to aggressive state of metastatic castration-resistant prostate cancer (mCRPC), wherein multiple therapeutic options demonstrate limited success rates. In this observational study, we aimed to evaluate the efficacy, toxicity, and survival outcomes of (a) [225Ac]Ac-PSMA-617, (b) rechallenge [177Lu]Lu-PSMA-617, (c) cabazitaxel, a…
Parihar AS, Dehdashti F, Pant N, Ravindra SG et al.
Prostate Cancer Working Group 4 recommends using prostate-specific membrane antigen (PSMA) PET for response assessment of patients with androgen pathway receptor modulator-resistant prostate cancer treated with 177Lu-PSMA-617. For that purpose, the time interval between baseline PSMA PET and initiation of therapy is critical as interim disease progression may influence the perf…
Eighteen-minute 360° cadmium zinc telluride (CZT) total-body 177Lu-labeled SPECT acquisitions on the single 113-keV 177Lu photopeak (SP-18) have been reported to be suitable for monitoring [177Lu]Lu-PSMA therapy. This study evaluated dual-energy 113- and 208-keV acquisitions with a more than 2-fold increase in acquired counts, allowing acquisition time to be reduced to 9 min (D…
Ranzani M, Cicconi A, Sastre-Moreno G, Thapa A et al.
PurposeRadioligand therapy (RLT) delivers radionuclides, such as Lutetium-177 (177Lu), to selectively target cancer cells. Despite the favourable clinical outcomes of 177Lu-based RLT, complete cure remains infrequent. A comprehensive understanding of its mode of action (MoA) is essential for strategic design of novel combination approaches that could improve therapeutic respons…
Immanuel C, Büttner T, Sprinkart AM, Nowak S et al.
PurposeSkeletal muscle radiodensity (SMD) is an emerging imaging-derived marker of muscle quality. Its prognostic relevance in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy has not yet been systematically evaluated. This study aims to investigate the prognostic value of SMD derived from routine pretherape…
Gebreslassea K, Mansoori N, Loux T, Saghebi J et al.
Radiopharmaceutical therapy with 177Lu-PSMA-617 is an established treatment for metastatic castration-resistant prostate cancer. Because the radiotracer is cleared renally, the kidneys receive measurable radiation exposure, requiring routine monitoring of renal function before each treatment cycle and after therapy. Understanding renal function trends during successive cycles, …
PurposeRecent clinical advances highlight 177Lu-PSMA-617 radioligand therapy as a promising option for treating prostate tumors. However, drug transport mechanisms and optimization of delivery strategies remain major challenges. In this study, we developed a multiscale computational model to analyze radioligand dynamics in prostate tumors and provide insights for improving ther…
Lutetium-177-labeled prostate-specific membrane antigen radioligand therapy (¹⁷⁷Lu-PSMA-RLT) emerged as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) following FDA approval in 2022. Its role in metastatic hormone-sensitive prostate cancer (mHSPC) is under active investigation. This systematic review synthesizes evidence on the efficacy, safety, a…
To improve the theranostic efficacy of PSMA-targeted radiopharmaceuticals on patients with medium-to-low PSMA expression, we radiolabeled a series of novel designed PSMA-targeting dimer agents to improve tumor imaging and treatment outcomes under challenging conditions. All agents were successfully radiolabeled with 68Ga in moderate decay-corrected labeling yield and high radio…
We investigated the prognostic value of baseline [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT in patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA-617. Methods: In this multicenter retrospective study, the associations between several clinical, biologic, and radiologic parameters and overall survival (OS) were tested in a development cohort using…
The prevalence, clinical impact, and clonal dynamics of clonal hematopoiesis (CH) in patients receiving 177Lu-PSMA-617 (LuPSMA) for metastatic castration-resistant prostate cancer (mCRPC) are unknown. Methods: Targeted next-generation sequencing of 21 genes recurrently mutated in CH was performed on DNA extracted from the peripheral blood of patients who received at least 4 cyc…
PurposeLutetium-177(177Lu)-PSMA-617 improves survival for patients with metastatic castration-resistant prostate cancer (mCRPC), but outcomes are heterogeneous and standardized risk stratification tools are lacking. We developed a novel risk stratification tool for patients treated with 177Lu-PSMA-617.MethodsWe conducted a retrospective analysis of 163 patients at Emory Winship…
[177Lu]Lu-PSMA-617 was approved after the VISION trial demonstrated significant benefit in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated outcomes of [177Lu]Lu-PSMA-617 with or without concurrent Androgen Receptor Pathway Inhibitors (ARPI) in a real-world setting. We retrospectively analyzed electronic health records of mCRPC patients treated with…
Al-Ibraheem A, Moghrabi S, Al-Houwari RM, Al-Qasem S et al.
Radiotheranostics is reshaping precision oncology by integrating molecular imaging with targeted radionuclide therapy through matched diagnostic-therapeutic radiopharmaceutical pairs. Landmark clinical successes, including Lutetium-177-DOTATATE (177Lu-DOTATATE) and 177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617), have validated this approach and accelerated the sh…
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