Search Results (70)

Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite advancements, the overall survival rate for lung cancer remains between 10% and 20% in most countries. However, recent progress in diagnostic tools and therapeutic strategies has led to meaningful improvements in survival outcomes, highlighting the growing importance of personalized management based on accurate disease assessment. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has become essential in the management of lung cancer, serving as a key imaging modality for initial diagnosis, staging, treatment response assessment, and follow-up evaluation. Recent developments in radiomics and artificial intelligence (AI), including machine learning and deep learning, have revolutionized the analysis of complex imaging data, enhancing the diagnostic and predictive capabilities of FDG PET/CT in lung cancer. However, the limitations of FDG, including its low specificity for malignancy, have driven the development of novel oncologic radiotracers. One such target is fibroblast activation protein (FAP), a type II transmembrane glycoprotein that is overexpressed in activated cancer-associated fibroblasts within the tumor microenvironment of various epithelial cancers. As a result, FAP-targeted radiopharmaceuticals represent a novel theranostic approach, offering the potential to integrate PET imaging with radioligand therapy (RLT). In this review, we provide a comprehensive overview of FDG PET/CT in lung cancer, along with recent advances in AI. Additionally, we discuss FAP-targeted radiopharmaceuticals for PET imaging and their potential application in RLT for the personalized management of lung cancer. Full article

Targeted radioligand therapy (RLT) is an emerging field in anticancer therapeutics with great potential across tumor types and stages of disease. While much progress has focused on agents targeting somatostatin receptors and prostate-specific membrane antigen (PSMA), the same advanced radioconjugation methods and molecular targeting have spurred the development of numerous theranostic combinations for other targets. A number of the most promising agents have progressed to clinical trials and are poised to change the landscape of positron emission tomography (PET) imaging. Here, we present recent data on some of the most important emerging molecular targeted agents with their exemplar clinical images, including agents targeting fibroblast activation protein (FAP), hypoxia markers, gastrin-releasing peptide receptors (GRPrs), and integrins. These radiopharmaceuticals share the promising characteristic of being able to image multiple types of cancer. Early clinical trials have already demonstrated superiority to ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) for some, suggesting the potential to supplant this longstanding PET radiotracer. Here, we provide a primer for practicing radiologists, particularly nuclear medicine clinicians, to understand novel PET imaging agents and their clinical applications, as well as the availability of companion targeted radiotherapeutics, the status of their regulatory approval, the potential challenges associated with their use, and the future opportunities and perspectives. Full article

Nuclear medicine has emerged as a critical modality in the diagnostic and therapeutic management of urological malignancies, particularly prostate cancer. Advances in single-photon emission computed tomography/computed tomography (CT) and positron emission tomography/CT (PET/CT) have enhanced tumor assessment across staging, treatment response, and recurrence settings. Molecular imaging, which offers insights beyond traditional anatomical imaging, is increasingly integral in specific clinical scenarios. Theranostic nuclear medicine, which combines diagnostic imaging with targeted therapy, has become a well-established treatment option, particularly for patients with metastatic castration-resistant prostate cancer (mCRPC). The development of the prostate-specific membrane antigen (PSMA) radioligands has revolutionized clinical management by enabling precise disease staging and delivering effective radioligand therapy (RLT). Ongoing research aims to refine the role of PSMA PET imaging in staging and treatment monitoring, while optimizing PSMA-targeted RLT for broader clinical use. Given that prostate cancer remains highly prevalent, the anticipated increase in the demand for RLT presents both challenges and opportunities for nuclear medicine services globally. Theranostic approaches exemplify personalized medicine by enabling the tailoring of treatments to individual tumor biology, thereby improving survival outcomes and maintaining patients’ quality of life with minimal toxicity. Although the current focus is on advanced disease, future research holds promise for expanding these strategies to earlier stages, potentially enhancing curative prospects. This evolving field not only signifies a paradigm shift in the care of prostate cancer patients but also underscores the growing importance of nuclear medicine in delivering precision oncology. Full article

Background/Objectives: Patients with metastatic castration-resistant prostate cancer (mCRPC) who have Prostate-Specific Membrane Antigen (PSMA)-negative disease have inferior outcomes with radioligand therapy (RLT). The objective of this study is to assess the added value of whole-body (WB) diffusion-weighted imaging (DWI) to PSMA PET for identifying PSMA-negative disease, which is important for risk stratification. Methods: Consecutive PSMA PET/MRI exams at our institution, which included WB DWI in patients with mCRPC, were retrospectively reviewed. For both WB DWI and PSMA PET, two independent readers scored 14 anatomic locations, which were considered positive only if both readers identified lesions. The proportion of patients with mismatched disease was summarized descriptively for each anatomic location and overall. The inter-reader agreement was computed with intra-class correlation coefficients (ICCs). Results: The study included 41 patients (with a mean age of 71.9 years), and WB DWI identified PSMA-negative lesions in 24% of patients. PSMA PET had higher agreement than DWI, although both had good agreement (ICC: 0.87 and 0.72, respectively). The median overall survival was 442 days in those with mismatched disease vs. 523 days in those without, although this difference is not statistically significant (p = 0.49). Conclusions: The addition of WB DWI to PSMA PET can identify PSMA-negative disease, which could alter patient management. Full article

Objectives: Metastatic castration-resistant prostate cancer (mCRPC) is associated with poor prognosis, particularly in cases of liver metastases. ¹⁷⁷Lu-PSMA-617 (commercially known as Pluvicto) is an FDA-approved radioligand therapy for mCRPC patients. This study aimed to evaluate the efficacy of ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients with liver metastases, focusing on progression-free survival (PFS), overall survival (OS), and factors influencing treatment response. Materials and Methods: This retrospective study included mCRPC patients (n = 32) with liver metastases treated with Lu-PSMA-617. Patient data, including prostate-specific antigen (PSA) levels, liver SUVmax values, Lutetium-PSMA therapy cycles, and survival outcomes, were collected. Kaplan–Meier survival analysis was used to calculate PFS and OS, while regression analysis was employed to identify factors associated with treatment response. Results: The median PFS and OS were 6 and 9 months, respectively. Partial regression was observed in patients with significantly lower PSA levels (median: 90.0 ng/mL, range: 22–699 ng/mL, p = 0.001) and liver SUVmax values (median: 17.9, range: 8.3–57.0, p = 0.008). A higher number of Lutetium-PSMA cycles correlated with improved treatment response (p = 0.010) and reduced liver SUVmax values (p = 0.043). Conclusions: Lu-PSMA-617 therapy is effective in managing mCRPC with liver metastases. Increased intensity of therapy exposure, reflected by a higher number of treatment cycles, is associated with a greater biochemical response, as indicated by reduced PSA levels, thereby supporting the rationale for personalized treatment strategies. These findings support the use of Lu-PSMA-617 in mCRPC patients with liver metastases, warranting further prospective studies. Full article

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [⁶⁸Ga]- and [¹⁸F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care. Full article

Background/Objectives: Radioligandtherapy (RLT) with [177Lu]Lu-PSMA has been newly introduced as a routine treatment for metastatic castration-resistant prostate cancer (mCRPC). However, not all patients can tolerate the entire therapeutic sequence, and in some cases, the treatment may prove ineffective. In real-world conditions, the aim is to distinguish between patients who fully benefit from treatment (those who respond effectively and tolerate the entire therapeutic sequence) and those who do not respond or cannot tolerate the entire sequence. This study explores predictive factors to distinguish between fully beneficial RLT treatment patients (FBTP) and not fully beneficial RLT treatment patients (NFBTP). The objective was to enhance the understanding of predictive factors influencing RLT effectiveness and to highlight the significance of machine learning in optimizing patient selection for treatment planning. Methods: Data from 25 mCRPC patients, categorized as FBTP (11) or NFBTP (14) to RLT, were analyzed. The dataset included clinical, imaging, and biological parameters. Data analysis techniques, including exploratory data analysis and feature engineering, were used to develop machine learning models for predicting patient outcomes. Results: Imaging data analysis revealed statistically significant differences in the renal uptake intensity of Choline between the two groups. A discordance of FDG+ and PSMA− was identified as a potential indicator of NFBTP. The integration of biological data enhanced the model’s predictive capability, achieving an accuracy of 0.92, a sensitivity of 0.96, and a precision of 0.96. Adding blood parameters like neutrophils, leukocytes, and alkaline phosphatase greatly increased prediction accuracy. Conclusions: This study emphasizes the significance of an integrated approach that merges imaging and biological data, thereby augmenting the predictive accuracy of patient outcomes in RLT with [177Lu]Lu-PSMA. In particular, including Choline PET among the imaging parameters provides unique insights into the predictive factors affecting RLT efficacy. This approach not only deepens the understanding of predictive factors but also underscores the utility of machine learning in refining the patient selection process for optimized treatment planning. Full article

Background/Objectives: The augmentation of [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [²²⁵Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [¹⁸F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUV_max, SUV_peak, SUV₅, SUV_mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [¹⁸F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [²²⁵Ac]Ac-PSMA-617 augmented [¹⁷⁷Lu]Lu-PSMA-617 RLT after insufficient response to [¹⁷⁷Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [¹⁸F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC. Full article

Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [¹⁷⁷Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [¹⁷⁷Lu]Lu-DOTA-TATE and 1.85 GBq [⁹⁰Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. Full article

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. Methods: A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. Results: PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Conclusions: Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC. Full article

Background: Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing. Methods: Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS). Results: Fifty-nine cases were included. PFS was similar in the PRRT (n = 29) and CAPTEM (n = 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99; p = 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months; p = 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months; p = 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months; p = 0.02). ORR did not vary significantly (34.78% vs. 40.91%; p = 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months; p = 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20; p = 0.75). Conclusions: PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients with MEN1, DAXX, and/or ATRX mutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR. Full article

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28–0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33–1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients. Full article

The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [⁶⁸Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [¹⁷⁷Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUV_max), the mean standardized uptake value of all tumor lesions (SUV_mean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann–Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUV_mean of all lesions was significantly different between responders and non-responders (SUV_mean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUV_mean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT. Full article

Introduction: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of ¹⁷⁷Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. Methods: An extensive literature search was performed in three different databases using different combinations of the following terms: “Lu-PSMA”, “¹⁷⁷Lu-PSMA”, “preclinical”, “mouse”, “salivary gland cancer”, “breast cancer”, “glioblastoma”, “solid tumour”, “renal cell carcinoma”, “HCC”, “thyroid”, “salivary”, “radioligand therapy”, and “lutetium-177”. The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. Results: A total of four preclinical studies were selected (breast cancer model n = 3/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. Conclusions: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer. Full article

In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that ¹⁷⁷Lu-PSMA-617 as monotherapy was more effective for the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Four past and present RCTs included 1081 patients. An RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and ¹⁷⁷Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed ¹⁷⁷Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value < 6.9 × 10⁻⁶). Conclusions: Patients with PCa gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies. Full article