Radiosynthesis and Preclinical Evaluation of [68Ga]Ga-NOTA-Folate for PET Imaging of Folate Receptor β Positive Macrophages
| العنوان: | Radiosynthesis and Preclinical Evaluation of [68Ga]Ga-NOTA-Folate for PET Imaging of Folate Receptor β Positive Macrophages |
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| المؤلفون: | Meeri Käkelä, Jenni Virta, Heidi Liljenbäck, Juhani Knuuti, Fenghua Zhang, Tuula Tolvanen, Tiit Örd, Xiang-Guo Li, Petri Elo, Merja Heinäniemi, Minna U. Kaikkonen, Maxwell G. Miner, Senthil Palani, Madduri Srinivasarao, Olli Moisio, Päivi Marjamäki, Erika Atencio Herre, Antti Saraste, Philip S. Low, Anne Roivainen |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Biodistribution, lcsh:Medicine, Gallium Radioisotopes, Inflammation, CHO Cells, Article, 030218 nuclear medicine & medical imaging, Heterocyclic Compounds, 1-Ring, Mice, 03 medical and health sciences, chemistry.chemical_compound, Cricetulus, Folic Acid, 0302 clinical medicine, Fluorodeoxyglucose F18, Glucosamine, Cricetinae, Positron Emission Tomography Computed Tomography, medicine, Animals, Humans, Tissue Distribution, Folate Receptor 2, lcsh:Science, Multidisciplinary, Macrophages, Small molecules, lcsh:R, Radiosynthesis, Histology, Translational research, Molecular biology, Effective dose (pharmacology), Plaque, Atherosclerotic, Rats, 030104 developmental biology, chemistry, Folate receptor, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Immunohistochemistry, lcsh:Q, Radiopharmaceuticals, medicine.symptom, 030217 neurology & neurosurgery, Ex vivo, Immunostaining |
| الوصف: | Folate receptor β (FR-β) is one of the markers expressed on macrophages and a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). First, we determined the affinity of 68Ga-FOL using human FR-β expressing cells. Then, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. After sacrifice, the tissues excised were measured with a γ-counter for ex vivo biodistribution. Further, the tracer distribution and co-localization with macrophages in aorta cryosections were studied using autoradiography, hematoxylin-eosin staining and immunostaining with anti-Mac-3 antibody. Specificity of 68Ga-FOL was assessed in a blocking study with excess of folate glucosamine. As a last step, human radiation doses were extrapolated from rat PET data. We were able to produce 68Ga-FOL at high radioactivity concentration, with high molar activity and radiochemical purity. The cell binding studies showed high (5.1 ± 1.1 nM) affinity of 68Ga-FOL to FR-β. The myocardial uptake of 68Ga-FOL (SUV 0.43 ± 0.06) was 20-folds lower compared to 18F-FDG (SUV 10.6 ± 1.8, P = 0.001). The autoradiography and immunohistochemistry of aorta revealed that 68Ga-FOL radioactivity co-localized with Mac-3-positive macrophage-rich atherosclerotic plaques. The plaque-to-healthy vessel wall ratio of 68Ga-FOL (2.44 ± 0.15) was significantly higher than that of 18F-FDG (1.93 ± 0.22, P = 0.005). Blocking studies verified 68Ga-FOL specificity to FR. As estimated from rat data the human effective dose was 0.0105 mSv/MBq. The organ with highest absorbed dose was kidney (0.1420 mSv/MBq). In conclusion, 68Ga-FOL is a promising new FR-β-targeted tracer for imaging macrophage-associated inflammation.TABLE OF CONTENT/ABSTRACT GRAPHIC |
| DOI: | 10.1101/2020.05.18.102483 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fda61709e805e7aed5710ef2a78b1b9 https://doi.org/10.1101/2020.05.18.102483 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3fda61709e805e7aed5710ef2a78b1b9 |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1101/2020.05.18.102483 |
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