Search Results (279)

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

This narrative review explores the integration of theranostics and artificial intelligence (AI) in neuro-oncology, addressing the urgent need for improved diagnostic and treatment strategies for brain tumors, including gliomas, meningiomas, and pediatric central nervous system neoplasms. A comprehensive literature search was conducted through PubMed, Scopus, and Embase for articles published between January 2020 and May 2025, focusing on recent clinical and preclinical advancements in personalized neuro-oncology. The review synthesizes evidence on novel theranostic agents—such as Lu-177-based radiopharmaceuticals, CXCR4-targeted PET tracers, and multifunctional nanoparticles—and highlights the role of AI in enhancing tumor detection, segmentation, and treatment planning through advanced imaging analysis, radiogenomics, and predictive modeling. Key findings include the emergence of nanotheranostics for targeted drug delivery and real-time monitoring, the application of AI-driven algorithms for improved image interpretation and therapy guidance, and the identification of current limitations such as data standardization, regulatory challenges, and limited multicenter validation. The review concludes that the convergence of AI and theranostic technologies holds significant promise for advancing precision medicine in neuro-oncology, but emphasizes the need for collaborative, multidisciplinary research to overcome existing barriers and enable widespread clinical adoption. 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

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer. Full article

Zirconium-89 (⁸⁹Zr) is a widely used radionuclide in immune-PET imaging due to its physical decay characteristics. Despite its importance, the production of ⁸⁹Zr radiopharmaceuticals remains largely manual, with limited cost-effective automation solutions available. To address this, we developed an automated system for the agile and reliable production of radiopharmaceuticals. The system performs transmutations, dissolution, and separation for a range of radioisotopes. Steps in the production of ⁸⁹Zr-oxalate are used as an exemplar to illustrate its use. Three-dimensional (3D) printing was exploited to design and manufacture a target holder able to include solid targets, in this case an ⁸⁹Y foil. Spot welding was used to attach ⁸⁹Y to a refractory tantalum (Ta) substrate. A commercially available CPU chiller was repurposed to efficiently cool the metal target. Furthermore, a commercial resin (ZR Resin) and compact peristaltic pumps were employed in a compact (10 × 10 × 10 cm³) chemical separation unit that operates automatically via computer-controlled software. Additionally, a standalone 3D-printed unit was designed with three automated functionalities: photolabelling, vortex mixing, and controlled heating. All components of the assembly, except for the target holder, are housed inside a commercially available hot cell, ensuring safe and efficient operation in a controlled environment. This paper details the design, construction, and modelling of the entire assembly, emphasising its innovative integration and operational efficiency for widespread radiopharmaceutical automation. Full article

Nanoradiopharmaceuticals integrate nanotechnology with nuclear medicine to enhance the precision and effectiveness of radiopharmaceuticals used in diagnostic imaging and targeted therapies. Nanomaterials offer improved targeting capabilities and greater stability, helping to overcome several limitations. This review presents a comprehensive overview of the fundamental design principles, radiolabeling techniques, and biomedical applications of nanoradiopharmaceuticals, with a particular focus on their expanding role in precision oncology. It explores key areas, including single- and multi-modal imaging modalities (SPECT, PET), radionuclide therapies involving beta, alpha, and Auger emitters, and integrated theranostic systems. A diverse array of nanocarriers is examined, including liposomes, micelles, albumin nanoparticles, PLGA, dendrimers, and gold, iron oxide, and silica-based platforms, with an assessment of both preclinical and clinical research outcomes. Theranostic nanoplatforms, which integrate diagnostic and therapeutic functions within a single system, enable real-time monitoring and personalized dose optimization. Although some of these systems have progressed to clinical trials, several obstacles remain, including formulation stability, scalable manufacturing, regulatory compliance, and long-term safety considerations. In summary, nanoradiopharmaceuticals represent a promising frontier in personalized medicine, particularly in oncology. By combining diagnostic and therapeutic capabilities within a single nanosystem, they facilitate more individualized and adaptive treatment approaches. Continued innovation in formulation, radiochemistry, and regulatory harmonization will be crucial to their successful routine clinical use. Full article

Neuroendocrine neoplasms (NENs) represent a heterogenous group of tumors with significant inter- and intra-patient variability. Once considered to be rare, neuroendocrine neoplasms are being increasingly recognized through the advent of advanced diagnostic techniques, which may be contributing to the significant increase in the incidence and detection rate of these tumors. NENs can be classified into well differentiated and poorly differentiated neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs). The proliferation rate of NETs can vary from Ki-67 1–55%. In addition, the SSTR expression can vary significantly. Because of this high “heterogeneity”, their detection and characterization have become essential to disease management, leading to dual-tracer imaging, most commonly with FDG- and SSTR-targeted PET/CT. Because of the complexity of the disease, the optimal treatment of patients depends on a combination of imaging, serological biomarkers, and clinical information. There remains a significant portion of patients who do not respond as anticipated, and the management of their disease remains challenging with current techniques, necessitating the refinement of our technologies and the development of new ones. In addition to new biological targets, improved peptide vector targeting for the somatostatin receptor needs further development. This review aims to evaluate the existing imaging techniques utilized in the diagnosis, assessment, and treatment of NENs, as well as the emerging radiopharmaceuticals and technologies, which will expand our imaging repertoire as well as our management options. Full article

The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [⁶⁸Ga]Ga-PSMA-11 PET and [¹⁷⁷Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [⁶⁸Ga]Ga-PSMA-11 PET imaging and downstream [¹⁷⁷Lu]Lu-PSMA-617 therapy remains imperfect. This suggests that prostate cancer theranostics could potentially be further refined through the implementation of true theranostics, tandem pairs of diagnostic and therapeutic radiopharmaceuticals that utilize the same ligand and element, thus yielding identical pharmacokinetics. The radioscandiums are one such group of true theranostic radiopharmaceuticals. The radioscandiums consist of two β+ emitting scandium isotopes (⁴³Sc/⁴⁴Sc), as well as a β⁻ emitting therapeutic isotope (⁴⁷Sc), which can all conjugate with PSMA-targeting PSMA-617. This potential has led to extensive investigations into the production of the radioscandiums as well as pre-clinical assessments with several ligands; however, there is a lack of literature extensively describing the complete synthesis of scandium radiopharmaceuticals. which therefore limits the accessibility of radioscandium research in theranostics. As such, this work aims to present an easily translatable protocol for the synthesis of [⁴³Sc]Sc-PSMA-617 from a [⁴²Ca]CaCO₃ starting material, including target formation, nuclear production via ⁴²Ca(d,n)⁴³Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling. Full article

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like ⁶⁴Cu-bevacizumab and ⁸⁹Zr-ramucirumab, has emerged as a powerful strategy for non-invasive imaging of VEGFR expression and distribution in vivo. Through positron emission tomography (PET) and single-photon emission computed tomography (SPECT), these targeted tracers enable real-time visualization of angiogenic and lymphangiogenic activity, providing insights into disease progression and therapeutic responses. This review explores the current advances in VEGFR-targeted imaging, focusing on the development of novel tracers, radiolabeling techniques, and their in vivo imaging characteristics. We discuss the preclinical and clinical applications of VEGFR imaging, highlight existing challenges, and provide perspectives on future innovations that could further enhance precision diagnostics and therapeutic monitoring in angiogenesis and lymphangiogenesis-driven diseases. Full article

Background/Objectives: Gliomas, including the most aggressive subtype—glioblastoma multiforme, are brain tumors with an unfavorable prognosis and high mortality. Early diagnosis is essential to improve treatment efficacy. Positron emission tomography PET with O-(2-[¹⁸F] fluoroethyl)-L-tyrosine ([¹⁸F]FET) has been supported by clinical studies for its role in diagnosis and monitoring the disease. However, the low availability of [¹⁸F]FET in Italy has limited its use in clinical praxis. This study describes the technological transfer of the radiopharmaceutical IASOglio^® (the commercial [¹⁸F]FET developed by Curium Pharma in Italy), with the aim of improving national access to this advanced diagnostic technology. Methods: Three consecutive batches were produced using the automated Trasis AllinOne module, and quality control was performed, including chemical and microbiological tests, to successfully validate the production process. Additionally, the stability of the radiopharmaceutical for its entire shelf life has been demonstrated with stability testing at 14 h after end of synthesis (EOS). Results: The production of [¹⁸F]FET achieved a non-corrected yield between 49% and 52%, with a corrected decay rate ranging from 73% to 79%. The process met the required quality specifications, including bio-burden control and filter integrity. The technological transfer was successfully completed, and production authorization was obtained from the Italian Medicines Agency (AIFA) for the Officina Farmaceutica of Institute of Clinical Physiology of the National Research Council (CNR-IFC) located in Pisa. Conclusions: Local production of [¹⁸F]FET in Italy marks a milestone in glioma diagnosis, thereby contributing to timely treatment and improved clinical outcomes. 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: To conduct a systematic review to evaluate the detection rates (DR) of the three FDA-approved PSMA-targeted radiopharmaceuticals in patients with recurrent prostate cancer. Methods: Two individuals systematically searched MEDLINE, ScienceDirect, and Cochrane Libraries (February 2025), and independently reviewed all results to identify studies reporting patient-level ⁶⁸Ga-PSMA-11, ¹⁸F-DCFPyL, or ¹⁸F-flotufolastat DR in ≥100 evaluable patients with recurrent prostate cancer. Sample-weighted means (SWM) of extracted DR were calculated. Results: Of 5059 published articles, 37 met our inclusion criteria, reporting data from 8843 patients undergoing ⁶⁸Ga-PSMA-11 (n = 27), ¹⁸F-DCFPyL (n = 8), or ¹⁸F-flotufolastat (n = 2) studies. Heterogeneity was noted across enrolled populations, particularly in prior treatments. ⁶⁸Ga-PSMA-11 studies recruited patients with marginally higher median PSA than ¹⁸F-DCFPyL or ¹⁸F-flotufolastat studies (median PSA ranged from 0.1 to 10.7, 0.2–2.5, and 0.6–1.1, respectively). Reported overall DR ranged from 25 to 91% for ⁶⁸Ga-PSMA-11, 49–86% for ¹⁸F-DCFPyL, and 73–83% for ¹⁸F-flotufolastat, with SWM of 71%, 66%, and 79%, respectively. Post-prostatectomy DR were reported in 18 articles, resulting in SWM DR of 58% for ⁶⁸Ga-PSMA-11 (n = 12), 55% for ¹⁸F-DCFPyL (n = 4), and 76% for ¹⁸F-flotufolastat (n = 2). Among post-radiotherapy patients, SWM were 87% for ⁶⁸Ga-PSMA-11 (n = 4), 90% for ¹⁸F-DCFPyL (n = 2), and 99% for ¹⁸F-flotufolastat (n = 1). SWM DR at PSA < 1 ng/mL were 53%, 42%, and 66% for ⁶⁸Ga-PSMA-11 (n = 13), ¹⁸F-DCFPyL (n = 5), and ¹⁸F-flotufolastat (n = 2), respectively. Conclusions: Considerable heterogeneity exists across populations in studies of diagnostic PET radiopharmaceuticals. Despite a paucity of ¹⁸F-DCFPyL and ¹⁸F-flotufolastat studies compared with ⁶⁸Ga-PSMA-11, the available data suggest that all three radiopharmaceuticals provide high overall DR in patients with biochemical recurrence of prostate cancer. Full article

Nuclear medicine (NM) procedures are performed using unsealed radioactive sources that are administered to patients, resulting in both internal and external exposure for patients and staff alike. Optimization is mainly concerned with ensuring the use of the lowest sufficient level of radiation to perform a procedure while maintaining adequate image quality. Diagnostic reference levels (DRLs) have been proven effective in aiding optimization in clinical practice. This dose review aims to establish an inclusive DRL system for the common adult NM procedures performed at Dubai Health. Our defined DRLs will focus on both the administered radiopharmaceuticals and the radiation dose metrics derived from hybrid computed tomography (CT). Dose surveys for 1439 adult nuclear medicine procedures performed over twelve months were collected and retrospectively analyzed. DRLs were obtained for a total of eight scintigraphy procedures, four hybrid positron emission tomography procedures with CT (denoted PET/CT), and five target sites for CT hybrid single-photon emission tomography with CT (denoted as SPECT/CT). Our derived DRLs for the scintigraphy, hybrid SPECT/CT and PET/CT procedures are within the reported national DRLs, except for the CT dose of the hybrid SPECT/CT for the neck, abdomen and chest/abdomen sites and the ¹⁸F PSMA administered activity. A fixed activity dose was administered for a scintigraphy procedure that is weight dependent. This patient dose review serves as a foundational effort aiming to optimize radiation safety and standardize diagnostic practices in NM. Further research is needed to enhance adherence to safety benchmarks. Full article

Background: While gallium-68 has traditionally dominated PET imaging in oncology, copper radionuclides have sparked interest for their potential applications in nuclear medicine and theranostics. Considering the advantageous physical decay properties of copper-61 compared to those of gallium-68, we describe a fully automated GMP-compliant synthesis process for ⁶¹Cu-based radiopharmaceuticals and demonstrate their in vivo application for targeting the overexpressed PSMA by PET/MR imaging. Methods: Copper-61 was obtained through the irradiation of natural zinc liquid targets in a biomedical cyclotron. [⁶¹Cu]Cu-DOTAGA-PSMA-I&T and [⁶¹Cu]Cu-NODAGA-PSMA-I&T were produced without manual intervention in two Synthera^® Extension modules. Radiochemical purity was analyzed by radio-HPLC and iTLC. Cellular uptake was evaluated in LNCaP and DU145 cells. In vivo PET/MRI was performed in control mice to evaluate the biodistribution of both radiopharmaceuticals, and in tumor-bearing mice to assess the targeting ability towards PSMA. Results: The fully automated process developed proved to be effective for the synthesis of ⁶¹Cu-based radiopharmaceuticals, with appropriate molar activities. The final products exhibited high radiochemical purity (>98%) and remained stable for up to 6 h after the EOS. A time-dependent increase in cellular uptake was observed in LNCaP cells, but not in DU145 cells. As opposed to [⁶¹Cu]Cu-NODAGA-PSMA-I&T, [⁶¹Cu]Cu-DOTAGA-PSMA-I&T exhibited poor kinetic stability in vivo. Subsequent PET/MR imaging with [⁶¹Cu]Cu-NODAGA-PSMA-I&T showed tumor uptake lasting up to 4 h post-injection, predominant renal clearance, and no detectable accumulation in non-targeted organs. Conclusions: These results demonstrate the feasibility of the implemented process, which yields adequate amounts of high-quality radiopharmaceuticals and can be adapted to any standard production facility. This streamlined approach enhances reproducibility and scalability, bringing copper-61 closer to widespread clinical use, to the detriment of the conventionally accepted gallium-68. 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