Current research topics in FAPI theranostics:a bibliometric analysis

Purpose: The study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy. Methods: A PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author’s country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated. Results: A total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control. Conclusion: FAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.</p

Current research topics in FAPI theranostics:a bibliometric analysis

Purpose: The study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy. Methods: A PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author’s country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated. Results: A total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control. Conclusion: FAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.</p

99mTc-anti-TNF-α antibody for the imaging of disease activity in pulmonary sarcoidosis

Infliximab, a monoclonal antibody directed against tumour necrosis factor (TNF)-α, is used in the treatment of refractory sarcoidosis. However, the clinical response is variable and a tool to select responders beforehand is highly desirable. In this study we evaluated scintigraphy with technetium-99m (99mTc)-labelled infliximab for the imaging of disease activity in patients with pulmonary sarcoidosis. 10 patients were studied using single photon emission computed tomography/computed tomography (CT) 6 h and 20 h after intravenous administration of 370 MBq of 99mTc-infliximab. Correlation analysis was performed between tissue accumulation of 99mTc-infliximab and laboratory parameters (including soluble interleukin-2 receptor and angiotensin-converting enzyme), lung function parameters (including forced expiratory volume in 1 s and the diffusing capacity of the lung for carbon monoxide) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Analysis showed selective and variable accumulation of 99mTc-infliximab in the target tissue. Accumulation correlated positively with all four laboratory parameters and negatively with all four lung function parameters, yielding better correlations than serum TNF-α levels or 18F-FDG PET/CT. 99mTc-infliximab accumulation reflects the in situ TNF-α expression in an individual patient and therefore provides valuable information on the presence of the biological target for anti-TNF-α therapy

Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis:A Pilot Study

Introduction: Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG(n=1–5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG(n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment. Methods: We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6–12 months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6–12 months of MTX therapy. MTXPG(n) concentrations were measured from whole blood RBC using an LC–MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship between changes in the SUVmax and MTXPG(n) concentrations. Results: We included 42 sarcoidosis patients treated with MTX (15 mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG3 and MTXPG4 a significant negative relation between the absolute changes in SUVmax and MTXPG(n) was found r = − 0.312 (n = 42, p = 0.047) for MTXPG3 and r = − 0.336 (n = 42, p = 0.031 for MTXPG4). The other MTXPG(n) did not correlate to changes in SUVmax. Conclusion: These results suggest a relation between MTXPG(n) concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine.</p