Search Results (108)

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

Background/Objectives: Fibroblast activation protein (FAP) is highly expressed in tumor stroma and selected inflammatory conditions, offering a promising target for molecular imaging. [⁶⁸Ga]Ga-FAPI-46 is a DOTA-based FAP inhibitor with excellent tumor-to-background ratio and potential advantages over [¹⁸F]FDG in low-glycolytic tumors. This article aims to highlight the quality elements that are relevant to clinical practice and to describe the development of an investigational medicinal product dossier for a bicentric clinical trial involving [⁶⁸Ga]Ga-FAPI-46. Methods: The radiolabeling was performed by the two facilities using different automated synthesizers, but with the same specifications and acceptance criteria Results: Three validation batches per site were analyzed for radiochemical/radionuclidic purity, pH, endotoxin, sterility, and bioburden according to European Pharmacopoeia standards. Stability was as sessed up to 2 h post-synthesis. All batches met predefined acceptance criteria. Conclusions: Despite differences in radiosynthesizer modules, product quality and process reproducibility were maintained across both centers. [⁶⁸Ga]Ga-FAPI-46 can be reliably produced in academic settings under GMP-like conditions, enabling multicenter clinical research and facilitating IMPD submissions for broader adoption of FAP-targeted PET imaging. Full article

Gallium-68 (⁶⁸Ga) radiopharmaceuticals are increasingly used in nuclear medicine due to their rapid production capabilities and exceptional specificity in molecular imaging applications. Several of these tracers have demonstrated remarkable clinical efficacy across various oncological conditions, including prostate cancer, neuro-endocrine tumours, and cancers expressing fibroblast activation protein. Commercial kits allow the use of the standardised production protocol, but extemporaneous preparations are the economic and flexible alternatives, particularly within hospital-based radiopharmacy settings. However, such preparations need meticulous conformity to quality control measures and regulation to ensure safety and effectiveness. This review provides an analysis of current methodologies employed in ⁶⁸Ga extemporaneous preparations and examines pertinent regulatory frameworks. Further clinical validation trials and technical advancement remain essential to facilitate the routine clinical practice’s widespread usage and long-term feasibility of such preparations. Full article

Background: Meta-analyses on the prevalence and significance of thyroid incidentalomas at PET (TIP) are available only about [¹⁸F]FDG. Focal TIP at [¹⁸F]FDG PET is not rare and may be malignant lesions in about one-third of cases. The aim of this study is to perform a meta-analysis on the prevalence and clinical significance of TIP using other PET radiotracers beyond [¹⁸F]FDG. Methods: A comprehensive literature search of studies about TIP was carried out using four different databases, screened until 31 December 2024. Only original articles about TIP using radiopharmaceuticals other than [¹⁸F]FDG were selected. A proportion meta-analysis on the prevalence and clinical significance of TIP was carried out on a patient-based analysis using a random-effects model. Results: 21 studies (29,409 patients) were included in the meta-analysis. PET was performed using radiolabeled somatostatin analogues (SSA) [n = 5], choline [n = 6], prostate-specific membrane antigen (PSMA) [n = 7], or fibroblast activation protein inhibitors (FAPI) [n = 3]. The uptake pattern of TIP was described as focal, diffuse, or mixed/heterogeneous. The pooled prevalence of TIP was 5.6% for SSA-PET, 6.1% for choline-PET, 4.2% for PSMA-PET, and 3.6% for FAPI-PET. The final diagnosis of TIP with a diffuse pattern was a benign condition or represented a physiological uptake. Conversely, TIP with focal or mixed/heterogeneous pattern may represent a benign condition in most cases, but even a malignant lesion in 6–10% of cases. Conclusions: As for [¹⁸F]FDG, TIP using other radiopharmaceuticals is not rare. Most of them are benign, but those with focal or heterogeneous uptake patterns may represent a malignant lesion in some cases (even if the risk of malignancy is lower compared to [¹⁸F]FDG PET), thus requiring further evaluation. Further studies are warranted to better clarify the clinical impact of TIP detection. Full article

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [⁶⁸Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients. Full article

Fibroblast activation protein (FAP) is a serine protease selectively expressed in cancer-associated fibroblasts (CAFs), fibrotic tissues, and areas of active tissue remodeling, making it an attractive target for diagnostic imaging across a spectrum of disease. FAP inhibitors (FAPIs) labeled with PET tracers have rapidly advanced as a novel imaging modality with broad clinical applications that offers several advantages, including rapid tumor accumulation, low background uptake, and high tumor-to-background ratios. In oncology, FAPI PET has demonstrated excellent performance in visualizing a wide range of malignancies, including those with low glycolytic activity, such as pancreatic cancer, cholangiocarcinoma, and certain sarcomas. Its high sensitivity and specificity for the stromal component enables improved tumor delineation, staging, and response assessment. Additionally, the potential to guide theranostic approaches, where the same tracer can be labeled with therapeutic radionuclides, positions FAPI as a key player in precision oncology. Beyond oncology, FAPI PET has shown promise in imaging conditions characterized by fibrotic and inflammatory processes. In the cardiovascular field, FAPI PET imaging is being investigated for its ability to detect myocardial fibrosis and active cardiac remodeling, crucial in conditions like heart failure, post-myocardial infarction remodeling, and hypertrophic cardiomyopathy. This review highlights the expanding clinical applications of FAPI-based PET imaging across oncology, inflammation, and cardiovascular disease. While the current data are promising, further large-scale studies and multicenter trials are essential to validate these findings and establish standardized protocols. The versatility and broad applicability of FAPI PET underscore its potential as a transformative tool in precision medicine. Full article

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multi-organ involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great potential to visualize in vivo fibrosis. We here provide an overview of available evidence on FAPi PET/CT imaging to visualize fibrosis in various IMIDs, including interstitial lung diseases, immunoglobulin G4-related diseases, cardiovascular diseases, kidney diseases, and gastrointestinal diseases. FAPi PET/CT imaging demonstrates high sensitivity in detecting early fibrosis, correlating with disease severity, across different IMIDs, showing superiority compared to conventional imaging modalities. Although FAPi PET/CT might be a useful tool to assess fibrosis formation, thereby aiding in grading disease severity and staging, future studies should include larger sample sizes in a broad variety of IMIDs with emphasis on the optimization of imaging protocols to further validate its diagnostic value. Full article

Gallium-labeled positron emission tomography (PET) probes targeting activated fibroblasts or somatostatin receptor expression are frequently used for varying applications in oncology. With the widespread availability of ⁶⁸Ge/⁶⁸Ga generators and cold kits, ⁶⁸Ga tracers have become a main tool in molecular imaging. These tracers, such as [⁶⁸Ga]Ga-DOTA-TATE, [⁶⁸Ga]Ga-FAPI, and [⁶⁸Ga]Ga-pentixafor, allow targeted imaging of the key pathological processes, including inflammation, fibrosis, and necrosis. This review highlights their potential in conditions like myocardial infarction, cardiac sarcoidosis, myocarditis, and other cardiomyopathies. Clinical and preclinical studies underscore their utility in visualizing active disease processes, predicting outcomes, and guiding therapeutic strategies. However, challenges remain, including the need for standardization, larger clinical trials, and integration into routine practice. These advancements position ⁶⁸Ga-based PET as a promising modality for enhancing diagnostic precision and personalized treatment in cardiovascular disease. Full article

Radiolabelled fibroblast activation protein inhibitor (FAPI) tracers have the potential to overcome the limitations of 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and improve the diagnosis and staging of hepato-pancreato-biliary (HPB) cancers. This study aims to compare the diagnostic performance of radiolabelled FAPI versus [¹⁸F]FDG PET imaging in HPB cancers. A systematic search of PubMed, Embase, Web of Science and Cochrane Library was performed to identify eligible studies on the diagnostic performance of FAPI PET for primary HPB tumours (hepatocellular carcinoma (HCC), pancreatic cancer (PC) and biliary tract cancer (BTC)) and for liver metastases of gastrointestinal origin. The diagnostic performance was defined as a combination of detection rate and semi-quantitative tracer uptake. A random-effects model was used to calculate the risk differences. In total, 28 studies were included. Histopathology was the reference standard for the primary tumour in 26 studies (93%). The detection rate of radiolabelled FAPI in comparison to [¹⁸F]FDG was significantly higher in HCC (0.33, 95% CI: 0.20–0.47 and 0.34, 95% CI: 0.23–0.45) and BTC (0.27, 95% CI: 0.11–0.43 and 0.28, 95% CI: 0.08–0.48), in the patient- and lesion-based analyses, respectively. In PC, no differences were observed. Radiolabelled FAPI outperformed [¹⁸F]FDG in the lesion-based detection of lymph node, liver and extra-hepatic metastases. In all HPB cancers, the mean SUVmax was significantly higher with radiolabelled FAPI compared to [¹⁸F]FDG. Molecular imaging with FAPI PET seems to have several benefits over [¹⁸F]FDG PET in HPB cancer diagnostics, with an overall higher tracer uptake, and higher detection rates in HCC and BTC. Full article

Background: Cancer-associated fibroblasts (CAFs) are key contributors to the tumorigenic process, with fibroblast activation protein (FAP) overexpressed on CAFs in numerous epithelial carcinomas. FAP represents a promising target for tumor imaging and therapy. We aimed to develop a novel [¹⁸F]AlF-H₃RESCA-FAPI radiotracer with a high labeling yield at room temperature for positron emission tomography (PET) imaging of FAP-expressing tumors. Methods: The H₃RESCA-FAPI chelator was synthesized and radiolabeled with [¹⁸F]AlF. Its radiotracer binding affinity to FAP was assessed using surface plasmon resonance (SPR). Its in vitro stability, plasma clearance, and biodistribution were evaluated. PET imaging was performed in U87MG tumor-bearing mice, with a blocking study to assess tracer specificity. Results: The [¹⁸F]AlF-H₃RESCA-FAPI radiotracer demonstrated a high binding affinity to FAP (K_D < 10.09 pM) and favorable radiochemical yields (92.4 ± 2.4%) with >95% radiochemical purity. In vitro and in vivo studies showed good stability and rapid clearance from non-target tissues. PET imaging revealed specific tumor uptake, which was significantly reduced by co-injection with unlabeled DOTA-FAPI-04. Conclusions: [¹⁸F]AlF-H₃RESCA-FAPI is a promising radiotracer for PET imaging of FAP-expressing tumors. Further optimization of its pharmacokinetics could make it a potential candidate for clinical translation. Full article

Background: This systematic review was performed to investigate the potential diagnostic role of fibroblast activation protein (FAP)-targeted radiopharmaceuticals in hepatocarcinoma (HCC) and cholangiocarcinoma (CCA). Methods: Relevant studies published between 2019 and 2023 were selected by searching PubMed and Scopus. The following data were extracted: authors, radiopharmaceuticals, sample size, country and year of publication, study design, and main results. Selected studies were analyzed using a modified version of the Critical Appraisal Skills Programme (CASP). Results: A total of 15 papers were finally selected, where 5 (33%) were retrospective, and 10 (67%) were prospective, with an overall number of 331 involved patients. Most of the studies (14/15, 93%) employed the FAP inhibitor series (FAPI), while only one research study used cyclic peptides as FAP-binding motifs. Twelve papers (80%) compared these FAP-targeted radiopharmaceuticals with ¹⁸F-FDG. The other 3/15 (20%) were not comparative studies and used exclusively ⁶⁸Ga-FAPI-04. ⁶⁸Ga-FAPI-04 is the most used radiopharmaceutical in analyzed studies (11/15, 73%), while other tracers, including ¹⁸F-FAPI, ⁶⁸Ga-FAPI-46, and ⁶⁸Ga-FAP-2286, were used in the remaining ones. Conclusions: FAP-targeted radiopharmaceuticals have good diagnostic accuracy in HCC and CCA, with potential and promising theragnostic applications. Full article

Background/Objectives: Over the past four years, ⁶⁸Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) has been established at a tertiary cancer care facility in Jordan. This retrospective study aims to explore tracer uptake metrics across various epithelial neoplasms, identify diagnostic pitfalls associated with ⁶⁸Ga-FAPI PET/CT, and evaluate the influence of ⁶⁸Ga-FAPI PET/CT staging results on changes in therapeutic intent compared to gold standard molecular imaging modalities. Methods: A total of 48 patients with biopsy-confirmed solid tumors underwent 77 ⁶⁸Ga-FAPI PET/CT examinations for molecular imaging assessment, encompassing neoplasms originating from the gastrointestinal tract, head and neck, hepatobiliary system, pancreas, breast, and lung. Results: Notably, pancreaticobiliary tumors exhibited the highest tracer uptake, with mean maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBR) surpassing 10. A comparative sub-analysis of ⁶⁸Ga-FAPI PET metrics in 20 treatment-naïve patients revealed a significant correlation between ⁶⁸Ga-FAPI uptake metrics and tumor grade (Spearman’s rho 0.83; p = 0.00001). Importantly, the results from ⁶⁸Ga-FAPI PET/CT influenced treatment decisions in 35.5% of the cases, primarily resulting in an escalation of management plans. A total of 220 diagnostic challenges were identified across 88.3% of the scans, predominantly within the musculoskeletal system, attributed to degenerative changes (99 observations). Conclusions: This comprehensive analysis highlights the potential significance of ⁶⁸Ga-FAPI PET/CT in oncological imaging and treatment strategy, while also emphasizing the necessity for meticulous interpretation to mitigate diagnostic challenges. Full article

Background: The role of molecular imaging in urothelial cancer is less defined than other cancers, and its utility remains controversial due to limitations such as high urinary tracer excretion, complicating primary tumour assessment in the bladder and upper urinary tract. This review explores the current landscape of PET imaging in the clinical management of urothelial cancer, with a special emphasis on potential future advancements including emerging novel non-¹⁸F FDG PET agents, PET radiopharmaceuticals, and PET-MRI applications. Methods: We conducted a comprehensive literature search in the PubMed database, using keywords such as “PET”, “PET-CT”, “PET-MRI”, “FDG PET”, “Urothelial Cancer”, and “Theranostics”. Studies were screened for relevance, focusing on imaging modalities and advances in PET tracers for urothelial carcinoma. Non-English language, off-topic papers, and case reports were excluded, resulting in 80 articles being selected for discussion. Results: ¹⁸F FDG PET-CT has demonstrated superior sensitivity over conventional imaging, such as contrast-enhanced CT and MRI, for detecting lymph node metastasis and distant disease. Despite these advantages, FDG PET-CT is limited for T-staging of primary urothelial tumours due to high urinary excretion of the tracer. Emerging evidence supports the role of PETC-CT in assessing response to neoadjuvant chemotherapy and in identifying recurrence, with a high diagnostic accuracy reported in several studies. Novel PET tracers, such as ⁶⁸Ga-labelled FAPI, have shown promising results in targeting cancer-associated fibroblasts, providing higher tumour-to-background ratios and detecting lesions missed by traditional imaging. Antibody-based PET tracers, like those targeting Nectin-4, CAIX, and uPAR, are under investigation for their diagnostic and theranostic potential, and initial studies indicate that these agents may offer advantages over conventional imaging and FDG PET. Conclusions: Molecular imaging is a rapidly evolving field in urothelial cancer, offering improved diagnostic and prognostic capabilities. While ¹⁸F FDG PET-CT has shown utility in staging, further prospective research is needed to establish and refine standardised protocols and validate new tracers. Advances in theranostics and precision imaging may revolutionise urothelial cancer management, enhancing the ability to tailor treatments and improve patient outcomes. Full article