Search Results (221)

Prostate-specific membrane antigen (PSMA) is an essential zinc-dependent metalloprotease classified within the type II transmembrane protein family, often referred to as glutamate carboxypeptidase II (GCPII). PSMA is recognized as a particularly promising target for both the diagnosis and therapeutic intervention of prostate cancer. In this study, we designed and synthesized PSMA-targeted DOTA-loaded bimodal conjugate 11 with SulfoCy5 fluorescent dye, performed in vitro characterization, and analyzed biodistribution in vivo. At 40–100 nM concentrations, the resulting conjugate demonstrated reliable visualization of tumor cells, on par with the reference PSMA-SylfoCy5 compound. In vivo biodistribution analysis of [⁶⁸Ga]Ga-11 in mice demonstrated a reduction in renal accumulation in comparison with dye-free conjugate [⁶⁸Ga]Ga-10. The specificity of [⁶⁸Ga]Ga-11 for PSMA was confirmed in a murine LNCaP xenograft model: its effective accumulation in tumors and kidneys, as well as relatively rapid elimination from non-target tissues, make it a promising agent for PET imaging but not radionuclide therapy. Full article

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article

Objective: This study aimed to evaluate the prognostic value of the SUVmax–IPI composite score, generated by integrating the maximum standardized uptake value (SUVmax) derived from metastatic ⁶⁸Ga-PSMA PET/CT imaging with the inflammatory prognostic index (IPI), in predicting overall survival in patients with metastatic prostate cancer. Materials and Methods: This retrospective, single-center cohort study included 146 patients diagnosed with metastatic prostate adenocarcinoma between 2009 and 2025. Among them, 125 patients with available PET/CT imaging were included in the SUVmax–IPI analysis. The composite score was calculated by multiplying the metastatic SUVmax value by the IPI. The optimal cut-off value was determined using receiver operating characteristic curve analysis. Overall survival was evaluated using the Kaplan–Meier method and compared using the log-rank test. Independent prognostic factors were identified using multivariable Cox proportional hazards regression analysis with a forward (stepwise) selection approach. Results: Using the predefined cut-off value (82), the median overall survival was 125 months in patients with SUVmax–IPI ≤ 82 and 19 months in those with SUVmax–IPI > 82 (log-rank p = 0.001). In the forward multivariable Cox regression model, SUVmax–IPI > 82 remained independently associated with worse overall survival after adjustment for ALP, AST, PSA nadir, and androgen deprivation modality (hazard ratio [HR]: 7.92; 95% confidence interval [CI]: 2.97–21.10; p < 0.001). Conclusions: The SUVmax–IPI composite score, integrating PSMA PET/CT-derived metabolic tumor activity with systemic inflammatory burden, is independently associated with overall survival in metastatic prostate cancer. These findings suggest that combining metabolic and inflammatory parameters may enhance prognostic stratification beyond conventional clinical and biochemical markers. Full article

Background: Precise staging of prostate cancer is vital for treatment planning and prognosis. While [⁶⁸Ga]Ga-PSMA-11 PET-CT has demonstrated high diagnostic accuracy in detecting metastatic disease, the interpretation of indeterminate or potentially benign PSMA-avid bone lesions remains a clinical challenge in routine practice. Methods: We conducted a retrospective single-centre study involving 214 patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET-CT between January 2021 and January 2024. Patients with prior known bone metastases or alternative PSMA radiotracers were excluded. Only those with follow-up imaging were included for diagnostic accuracy analysis. Follow-up modalities included PSMA PET-CT, CT, MRI, and bone scintigraphy. Final classification (metastatic or benign) was based on radiological and clinical assessment. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using follow-up imaging as the reference standard. Lesions classified as indeterminate were analysed separately and excluded from diagnostic performance calculations. Results: Of the 214 included patients, 142 had follow-up imaging. Among 80 patients with bone lesions initially reported as metastatic, 74 (92.5%) were confirmed. Among 28 patients initially reported as having benign bone lesions, 26 (92.9%) remained benign on follow-up. Thirty-four patients with indeterminate lesions were reviewed; four were ultimately metastatic. Excluding indeterminate cases, sensitivity, specificity, PPV, and NPV were 97.4%, 86.7%, 94.9%, and 92.9%, respectively. Diagnostic discordance was primarily associated with benign uptake in the ribs, iliac bones, pubic rami and degenerative changes. Conclusions: [⁶⁸Ga]Ga-PSMA-11 PET-CT shows excellent sensitivity and positive predictive value for detecting metastatic bone disease in prostate cancer. However, benign lesions may also exhibit uptake, emphasising the importance of integrating imaging results with PSA levels, Gleason scores, and TNM staging. Prospective studies are needed to validate these findings and assess their impact on long-term outcomes. Full article

Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials. Full article

Background: The PROSPET-BX trial compared [⁶⁸Ga]PSMA-11 PET/CT (PSMA-PET) with multiparametric MRI (mpMRI) in parallel in men with suspicion of prostate cancer (PCa) after at least one previously negative biopsy (ClinicalTrials.gov: NCT05297162; GR-2018-12366240). In this study, we performed the cost analysis of the two imaging modalities with respect to the detection of clinically significant PCa (csPCa). Methods: We analyzed the data from patients enrolled in the trial who met the inclusion criteria. For the cost analysis, we identified six competing triage strategies, each defined as a binary decision rule for referral to prostate biopsy: (1) biopsy-all; (2) elevated PSA-density (PSAD; biopsy if PSAD > 0.15 ng/mL/cc; (3) mpMRI positive (PIRADS 3–5); (4) PSMA-PET positive (PRIMARY 3–5); (5) mpMRI or PSMA-PET positive; (6) PSAD and mpMRI. For each strategy, we yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for csPCa. Direct hospital costs were modeled from a provider perspective, incorporating testing and procedural costs. Unit costs (in EUR) were sourced from our institutional accounting records. Pairwise cost-effectiveness comparisons were performed using incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB). Results: Among the six triage strategies evaluated, the “biopsy-all” approach achieved perfect sensitivity, whereas the PSAD + mpMRI pathway was the most parsimonious strategy but missed 14 csPCa cases (53.8%). The combined “mpMRI or PSMA-PET” strategy maximized detection (22 cPCa, missing only 4) at an intermediate cost (EUR 81.991 total; EUR 3.727 per csPCa). The pairwise comparison of each strategy with mpMRI alone showed for the mpMRI or PSMA-PET pathway a low ICER (~EUR 2.900/extra csPCa), with consistently positive and increasing INB across higher WTP (willingness-to-pay). Therefore, this combination provided the most favorable cost-effectiveness profile, balancing detection, efficiency, and cost. Conclusions: To the best of our knowledge, this is the first cost analysis study to compare different strategies incorporating PSMA-PET in the re-biopsy setting, demonstrating that the combined “mpMRI or PSMA-PET” pathway is the most cost-effective diagnostic pathway for csPCa detection. Full article

Background: The use of [⁶⁸Ga]Ga-PSMA-PET/CT for prostate cancer (PCa) staging is limited by cost and availability. This study evaluates whether radiomic features from contrast-enhanced (CE) CT can predict PSMA-positive lymph nodes (LNs) as a surrogate for metastasis. Methods: A retrospective study of 447 patients included 2537 segmented LNs (425 PET-positive, 2112 PET-negative). Two uroradiologists assessed 417 LNs on CE-CT using a four-point Likert scale. Radiomic features were extracted, selected using four algorithms, and analyzed with six model-building methods. Model performance was compared to radiologist ratings. Results: Radiomic models achieved an accuracy of 0.77–0.85, sensitivity of 0.85–0.91, and specificity of 0.74–0.85. Compared to radiologists, models had higher NPV (0.97–0.98 vs. 0.96) and sensitivity (0.85–0.91 vs. 0.76), but radiologists had superior accuracy (0.95 vs. 0.77–0.85) and specificity (0.97–0.98 vs. 0.74–0.85). In a subanalysis of LNs rated as probably benign or malignant, expert radiologists outperformed the algorithm with greater specificity and PPV (p < 0.005). A density threshold of >27 HU predicted PSMA-positive LNs with 0.79 accuracy, 0.87 sensitivity, and 0.78 specificity. Conclusions: While radiomics did not outperform expert radiologists, the single first-order parameter CT density >27 HU was predictive of PSMA-positive LNs. Clinical Relevance Statement: Radiomic models did not outperform expert uroradiologists. However, in high-volume or resource-limited settings lacking access to [⁶⁸Ga]Ga-PSMA-PET/CT, they may help improve LN assessment in PCa patients with CT alone. Full article

Prostate cancer (PCa) is the most common malignant tumor of the male genitourinary system, and its incidence and mortality have shown a marked global increase in recent years. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein highly expressed in PCa cells, has emerged as a vital molecular target in the field of PCa precision diagnosis and therapy. In recent years, significant advances have been achieved in PSMA-based molecular imaging, radioligand therapy, and the development of novel targeted drugs. This review aims to summarize and critically discuss recent advances in PSMA-targeted molecular imaging, radioligand therapy, and emerging therapeutic strategies, highlighting their roles in precision diagnosis and personalized treatment of PCa. PSMA positron emission tomography/computed tomography (PET/CT) imaging using radionuclides such as ⁶⁸Ga and ¹⁸F has markedly improved the accuracy of primary tumor staging, localization of recurrent lesions, and therapeutic response assessment. Radioligand therapies, such as ¹⁷⁷Lu-PSMA-617 and ²²⁵Ac-PSMA-617, have prolonged survival and demonstrated symptomatic benefits in multiple clinical trials, and are now applied in early disease stages, including chemotherapy-naïve and hormone-sensitive settings. Meanwhile, PSMA-targeted antibodies and antibody–drug conjugates (PSMA-ADCs), as well as bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, are constantly being optimized and show promising clinical potential. Furthermore, PSMA-targeted nanoplatforms enable precise delivery of chemotherapeutic agents, photosensitizers, or imaging probes, achieving integrated diagnosis and therapy with multimodal imaging guidance, and offering new strategies for individualized treatment. Taken together, the evidence summarized in this review highlights PSMA as a pivotal molecular target supporting precision diagnosis and personalized treatment across the continuum of prostate cancer management. Full article

Introduction: [¹⁸F]-DCFPyL (Piflufolastat [¹⁸F]) is a prostate-specific membrane antigen (PSMA)-targeted position emission tomography (PET) radiotracer for detecting the biochemical recurrence (BCR) of prostate cancer (PCa). This study evaluates its economic impact compared with [⁶⁸Ga]-PSMA-11, [¹⁸F]-FCH, and [¹⁸F]-PSMA-1007 from the Spanish National Healthcare System’s perspective. Methods: A cost–consequence model, over a 5-year time horizon, simulated the diagnostic and treatment pathway based on radiotracer-specific accuracy and disease localization. Treatment options included a radical prostatectomy, radiation therapy, androgen deprivation therapy (ADT), and radiation therapy + ADT. Costs were calculated for true/false positives and negatives. Due to limited data availability, key inputs were informed by expert opinions, supported by published meta-analyses, public sources, and literature. Officially published Spanish prices were applied: EUR 2000 for [¹⁸F]-DCFPyL, [⁶⁸Ga]-PSMA-11, and [¹⁸F]-PSMA-1007, and EUR 1144 for [¹⁸F]-FCH. Results: The use of [¹⁸F]-DCFPyL led to fewer unnecessary therapies; specifically, it led to 11,229 (74%) fewer than [⁶⁸Ga]-PSMA-11, and 5180 (56%) and 7771 (66%) fewer than [¹⁸F]-FCH and [¹⁸F]-PSMA-1007, respectively. It achieved significant cost savings for repeated testing: EUR 15M (43%) versus [⁶⁸Ga]-PSMA-11, EUR 37M (65%) versus [¹⁸F]-FCH, and EUR 27M (58%) versus [¹⁸F]-PSMA-1007. Cost savings for false positives were EUR 15M (50%) against [⁶⁸Ga]-PSMA-11, EUR 22M (60%) versus [¹⁸F]-FCH, and EUR 29M (66%) compared with [¹⁸F]-PSMA-1007. The cost per correct diagnosis was reduced by EUR 198 (8%) compared with [⁶⁸Ga]-PSMA-11 and EUR 377 (15%) relative to [¹⁸F]-PSMA-1007, while showing a EUR 635 (40%) increase compared with [¹⁸F]-FCH. Conclusions: [¹⁸F]-DCFPyL offers a cost-saving option for BCR detection within the Spanish National Healthcare System by reducing the number of unnecessary therapies, the cost of false positives, and repeat testing compared with alternative radiotracers. These improvements support the potential for better diagnostic outcomes and more informed downstream clinical decision-making. Full article

Recurrent brain tumors—including high-grade gliomas, brain metastases, and aggressive meningiomas—continue to carry a poor prognosis, with high mortality despite therapeutic advances. The aim of this narrative review is to summarize and critically discuss the current evidence on the role of intra-arterial radioligand therapy (RLT) in the treatment of recurrent brain tumors. RLT, a targeted form of radionuclide therapy, has gained increasing attention for its potential theranostic applications in neuro-oncology. A literature search was conducted using PubMed and Scopus, including clinical studies evaluating intra-arterial radioligand delivery in central nervous system tumors. Recent research has explored intra-arterial administration of radioligands targeting somatostatin receptors and prostate-specific membrane antigen (PSMA). Somatostatin receptors are overexpressed in meningiomas, while PSMA is highly expressed in the neovasculature of glioblastomas and brain metastases; both targets can be addressed using lutetium-177 (¹⁷⁷Lu)- or actinium-225 (²²⁵Ac)-labeled radiopharmaceuticals, traditionally delivered intravenously. Available evidence indicates that the intra-arterial route achieves markedly higher radionuclide uptake on ⁶⁸Ga-PSMA-11 and ⁶⁸Ga-DOTATOC PET, as well as increased absorbed doses in dosimetric models. Dosimetric analyses consistently show greater tracer accumulation compared with intravenous administration, without evidence of significant peri-procedural toxicity. Uptake in healthy brain tissue is minimal, and no relevant differences have been reported in liver or salivary gland accumulation between intra-arterial and intravenous RLT. Although based on heterogeneous and limited data, intra-arterial RLT appears to be a promising therapeutic strategy for recurrent brain tumors. Future research should focus on improving radioligand delivery beyond the blood–brain barrier and enhancing effective tumor targeting. Full article

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

Background: While prostate-specific membrane antigen (PSMA)-targeted imaging has revolutionized metastatic detection, unspecific bone uptake (UBU)—particularly in the ribs—is a common but diagnostically challenging finding in prostate cancer (PCa) patients. This review aims to synthesize current evidence on PSMA-avid rib lesions in PCa and to propose a structured approach for differentiating true metastases from benign mimics. Methods: A comprehensive literature search across PubMed, EMBASE, Scopus, and Web of Science identified relevant studies on PSMA imaging interpretation, tracer-specific patterns, rib lesion morphology, and clinical correlates. Data on uptake intensity, CT features, lesion number, location, tracer type, patient-specific risk factors, and follow-up behavior were extracted and analyzed. Results: Most solitary rib lesions are benign, particularly in low-risk patients or when located in the anterior/lateral arcs. Metastatic lesions are more likely to present as multiple foci, show cortical destruction on CT, exhibit high uptake intensity, and occur in patients with elevated PSA, high Gleason score, or ongoing androgen deprivation. ¹⁸F-PSMA-1007 is especially prone to UBU in the ribs compared to ⁶⁸Ga-PSMA-11. Based on these variables, we propose a clinical decision tree to guide interpretation of PSMA-avid rib lesions. Conclusions: Accurate interpretation of rib lesions on PSMA PET/CT requires a multimodal, context-sensitive approach. Our diagnostic decision tree guides precise differentiation of benign versus metastatic rib lesions, enhancing staging accuracy and clinical decision-making. Biomarker-guided therapies offer potential for personalized treatment, though rib-specific validation remains a critical need. Full article

Background/Objectives: To investigate the importance of ADC, SUVmax, and SUVmax/ADC values in the prognosis and biological behavior of prostate cancer. Methods: In this retrospective study, ADC measurements in diffusion MRI were made by two radiologists by correlating the lesions with the highest SUVmax value from Ga-68 PSMA PET/CT examinations of 81 patients with prostate cancer. The quantitative values were compared with histopathological grade, presence of perineural invasion, and lymph node and bone metastasis. Results: For D’Amico high-risk patients, a statistically significant difference among the ADC, SUVmax, and SUVmax/ADC measurements was reported (p < 0.001). Cut-off values were defined as 0.52 (×10⁻³ mm²/s) for ADC, 9.73 for SUVmax, and 20.28 for the SUVmax/ADC ratio (AUC = 0.887, 0.747, 0.817, respectively) for the high-risk categories. The Youden indices were 0.643, 0.405, and 0.437, respectively. In logistic regression, the SUVmax/ADC ratio was a significant predictor of the high-risk group (AUC = 0.844, p = 0.002), demonstrating superior performance to a model with individual ADC and SUVmax values (AUC = 0.796, p = 0.006). For the advanced-grade group, the SUVmax and SUVmax/ADC ratios differed significantly (p < 0.001). The CAPRA score showed significant correlations with all imaging biomarkers: negatively with ADC (rho = −0.456, p < 0.001) and positively with SUVmax (rho = 0.359, p = 0.001) and the SUVmax/ADC ratio (rho = 0.441, p < 0.001). The presence of perineural invasion had no significant correlation with any of the variables (p > 0.05). The presence of bone metastases and PSA and free PSA levels differed significantly (p = 0.003, p = 0.001, respectively). In the presence of lymph node metastasis, SUVmax and SUVmax/ADC ratios were found to be significant (p = 0.019, p = 0.01, respectively). In the survival (OS) analysis, a low ADC value was found to be associated with shorter survival (median OS: 61 vs. 106 months). Conclusions: Among advanced-grade and high-risk prostate cancer patients, ADC, SUVmax, and SUVmax/ADC values can be employed as alternative prognostic factors for predicting the biological behavior of the disease. Full article

Background/Objectives: Bladder cancer is characterized by high recurrence and progression rates, posing a challenge to current diagnostic and treatment strategies. This review aims to provide a comprehensive overview of emerging technologies, including novel PET tracers, AI-assisted cystoscopy, theragnostics, and molecular biomarkers. Methods: We performed a narrative review of the recent literature focusing on innovations in imaging, AI, theragnostics, and biomarker research relevant to bladder cancer diagnosis and management. Results: Several novel PET tracers, such as 68Ga-PSMA and fibroblast activation protein inhibitor (FAPI), demonstrated potential in improving detection sensitivity. AI-enhanced cystoscopy has shown promise in real-time lesion detection, while theragnostic agents enable combined diagnostic and therapeutic applications. Advances in molecular biomarkers, including circulating Tumor DNA (ctDNA) and gene expression signatures, offer new avenues for patient stratification and monitoring. Conclusions: Integration of advanced imaging, AI, theragnostics, and biomarker analysis may transform bladder cancer management, supporting personalized and more effective care strategies. Full article

The growing use of experimental radiopharmaceuticals for targeted radionuclide therapy (TRT) highlights the need for robust “in house” radiolabeling protocols. Among these, PSMA-ALB-56 is a PSMA ligand incorporating an albumin-binding moiety to enhance pharmacokinetics, which showed promise for prostate cancer treatment. This study investigated manual radiolabeling conditions of this vector molecule with lutetium-177 and developed a corresponding automated synthesis protocol. Manual experiments on low activities explored buffer systems and antioxidants, identifying sodium acetate buffer and L-methionine as optimal, achieving radiochemical purities above 97% with excellent stability over 48 h. However, when these conditions were transposed directly to an automated process on a GAIA^® module with activities > 2 GBq, radiochemical purity dropped below 70% due to significant radiolysis. This result emphasized that conditions optimized at low activities are not directly transferable to high-activity automated production, and highlighted the crucial role of antioxidant concentration. An optimized automated method was subsequently developed, integrating a solid-phase extraction purification step, higher antioxidant levels during radiolabeling and formulation, and a larger final product volume. These changes led to radiochemical purities above 98.9% and excellent product stability over 120 h for 3 test batches. The presence of high concentrations of methionine and ascorbic acid was essential to protect against radiolysis. This work underscores the importance of adjusting radiolabeling strategies during process scale-up and confirmed that antioxidant concentration is essential for successful ¹⁷⁷Lu radiolabeling. The optimized automated method developed here for [¹⁷⁷Lu]Lu-PSMA-ALB-56 may also be adapted to other radiopharmaceuticals in development for TRT. Full article