Betül Altunay

Background: Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as novel radiopharmaceutical agents for tumor diagnosis. Compared with [¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), which reflects glucose uptake in metabolically active regions, FAPIs mainly bind to the fibroblast activation protein (FAP), which is highly expressed in tumor-associated fibroblasts, forming a pronounced signal. Several studies suggested potential superiority of FAPI tracers above [¹⁸F]FDG-based imaging in a variety of tumor entities. In this systematic review, we focus on the comparison of FAPI-PET/CT and [¹⁸F]FDG-PET/CT in upper-abdominal tumors. Methods: Original research published from 1 January 2021 to 22 December 2024 was collected from the PubMed and Web of Science databases (CRD42025648267). This research included only clinical studies, excluding conference abstracts and case reports. The risk of bias was assessed with the QUADAS-2 tool, and all evaluation steps performed independently by three independent reviewers. A systematic quality assessment of the included studies was conducted based on the imaging performance of FAPI-PET/CT and [¹⁸F]FDG-PET/CT for pancreatic, liver, and gastric cancers. The meta-analysis used relative risk (RR) as the effect size, with bias assessed via the Peters test (p-value > 0.05). Cochran’s Q test and I-squared value are used to comprehensively evaluate the magnitude of heterogeneity. Analyses and data visualization were performed in R language. Results: The database search identified 3272 articles. After screening, 31 studies were included in this analysis. The original studies enrolled 1377 participants (M/F: 850/527; ages predominantly between 50 and 70). Of these, 939 patients were ultimately diagnosed with tumors (five cancer subtypes) and included in this analysis. Meta-analysis results showed that FAPI-PET/CT significantly surpassed [¹⁸F]FDG-PET/CT in the detection of primary lesions (RRs = 1.20 and 1.17), lymph nodes (RRs = 1.18 and 1.24), distant metastases (RRs = 1.22 and 1.51), peritoneal metastases (RRs = 1.31 and 2.22), and bone metastases (RRs = 1.16 and 1.23). The two imaging methods exhibit clear differences in diagnostic performance (sensitivity: 98% vs. 79%; specificity: 83% vs. 87%), and FAPI-PET/CT demonstrates high and stable diagnostic performance (RRs = 1.20 and 1.17). Conclusions: Compared with [¹⁸F]FDG-PET/CT, FAPI-PET/CT demonstrates significant advantages in detecting primary lesions, lymph nodes, distant metastases, and peritoneal and bone metastases in pancreatic, liver, and gastric cancers (RR > 1.0). Overall, FAPI-PET/CT shows better diagnostic performance (RR > 1.0).

BACKGROUND: Elevated levels of cardiac branched-chain amino acids (BCAAs) and their metabolites, namely branched-chain keto acids (BCKAs), contribute to the development of insulin resistance, contractile dysfunction, and adverse remodeling in the failing heart. However, there is still confusion about whether BCAA or BCKA mediate these detrimental effects in the failing heart. METHODS: Cardiac-specific mitochondrial branched-chain aminotransferase, the enzyme that converts BCAA into BCKA, knockout (BCAT2 ^{− /−} ) mice underwent a sham or transverse aortic constriction surgery to induce heart failure. Changes in cardiac function and structure were monitored pre- and posttransverse aortic constriction using echocardiography, and metabolic flux through the tricarboxylic acid cycle was measured by perfusing isolated working hearts with radiolabeled energy substrates. Direct effects of BCAA and BCKA on cell hypertrophy were characterized using phenylephrine-induced cell hypertrophy in differentiated cells. RESULTS: Lowering cardiac BCKA levels in BCAT2 ^−/− failing hearts increases insulin-stimulated glucose oxidation rates via enhancing mitochondrial protein kinase B and pyruvate dehydrogenase complex activities. Increased glucose oxidation rates in BCAT2 ^−/− failing hearts enhanced cardiac efficiency by decreasing myocardial oxygen consumption rates. However, cardiac BCAA accumulation was associated with excessive stimulation of the mammalian target of rapamycin signaling and aggravation of adverse cardiac remodeling in BCAT2 ^−/− failing hearts. As a result, the impact of BCAA accumulation offsets the beneficial effects of lowering cardiac BCKA levels on cardiac insulin sensitivity and cardiac efficiency. CONCLUSIONS: Lowering BCKA levels enhances cardiac glucose oxidation and cardiac efficiency by enhancing mitochondrial insulin signaling. BCAA accumulation worsens adverse cardiac remodeling by exacerbating cardiac mammalian target of rapamycin signaling.

In this narrative review, we aim to summarize recent advancements in nuclear molecular imaging techniques and their applications in BCa management. The main focus of this review is on the most relevant clinical investigations from the past 2–3 years that highlight the enhanced diagnostic and therapeutic value of these imaging modalities. A variety of radiolabeled probes introduced in molecular imaging is explored, detailing their roles in the accurate diagnosis and characterization of BCa, as well as their integration into radioligand therapy and theragnostic strategies.

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical cancer research, necessitating meticulous attention to radiotracer synthesis, quality assurance, and in vivo injection protocols. This study presents a comprehensive workflow tailored to enhance the robustness and reproducibility of small animal PET experiments. The synthesis process in the radiochemistry laboratory using 68Ga is detailed, highlighting stringent quality control and assurance protocols for each radiotracer production. Parameters such as concentration, molar activity, pH, and purity are rigorously monitored, aligning with standards applicable to human studies. This methodology introduces streamlined syringe preparation and a custom-designed 30G cannula for precise intravenous injections into mice. Monitoring of animal health during scanning, including temperature and heart rate, ensures their well-being throughout the procedure. Dosages for PET and SPECT scans are predetermined to balance data acquisition with minimizing radiation exposure to animals and researchers. Similarly, CT scans employ pre-programmed settings to limit radiation exposure, especially pertinent in long-term studies assessing treatment effects. By optimizing these steps, the workflow aims to standardize procedures, reduce variability, and enhance the quality of small animal PET/SPECT/CT imaging. This resource provides valuable insights for researchers seeking to improve the accuracy and reliability of preclinical investigations in molecular imaging, ultimately advancing the field.

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical cancer research, necessitating meticulous attention to radiotracer synthesis, quality assurance, and in vivo injection protocols. This study presents a comprehensive workflow tailored to enhance the robustness and reproducibility of small animal PET experiments. The synthesis process in the radiochemistry laboratory using 68Ga is detailed, highlighting stringent quality control and assurance protocols for each radiotracer production. Parameters such as concentration, molar activity, pH, and purity are rigorously monitored, aligning with standards applicable to human studies. This methodology introduces streamlined syringe preparation and a custom-designed 30G cannula for precise intravenous injections into mice. Monitoring of animal health during scanning, including temperature and heart rate, ensures their well-being throughout the procedure. Dosages for PET and SPECT scans are predetermined to balance data acquisition with minimizing radiation exposure to animals and researchers. Similarly, CT scans employ pre-programmed settings to limit radiation exposure, especially pertinent in long-term studies assessing treatment effects. By optimizing these steps, the workflow aims to standardize procedures, reduce variability, and enhance the quality of small animal PET/SPECT/CT imaging. This resource provides valuable insights for researchers seeking to improve the accuracy and reliability of preclinical investigations in molecular imaging, ultimately advancing the field.