Radiation dosimetry and biodistribution of 68Ga-FAPI-46 PET imaging in cancer patients

• Verfasst von: Meyer, Catherine [VerfasserIn]
• Verfasst von: Dahlbom, Magnus [VerfasserIn]
• Verfasst von: Lindner, Thomas [VerfasserIn]
• Verfasst von: Vauclin, Sébastien [VerfasserIn]
• Verfasst von: Mona, Christine [VerfasserIn]
• Verfasst von: Slavik, Roger [VerfasserIn]
• Verfasst von: Czernin, Johannes [VerfasserIn]
• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Verfasst von: Calais, Jérémie [VerfasserIn]
• Titel: Radiation dosimetry and biodistribution of 68Ga-FAPI-46 PET imaging in cancer patients
• Verf.angabe: Catherine Meyer, Magnus Dahlbom, Thomas Lindner, Sébastien Vauclin, Christine Mona, Roger Slavik, Johannes Czernin, Uwe Haberkorn, and Jérémie Calais
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 7 S.
• Fussnoten: Published online: December 13, 2019 ; Im Titel ist "68" hochgestellt ; Gesehen am 05.10.2020
• Titel Quelle: Enthalten in: Journal of nuclear medicine
• Ort Quelle: New York, NY : Soc., 1964
• Jahr Quelle: 2020
• Band/Heft Quelle: 61(2020), 8, Seite 1171-1177
• ISSN Quelle: 2159-662X
• ISSN Quelle: 1535-5667
• DOI: doi:10.2967/jnumed.119.236786
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Biodistribution
• Sach-SW: Dosimetry
• Sach-SW: FAPI
• Sach-SW: Gallium-68
• Sach-SW: PET/CT
• Sach-SW: Radiobiology/Dosimetry
• Sach-SW: Radiotracer Tissue Kinetics
• K10plus-PPN: 1734664746

Abstract

Background: Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy as they can constitute as much as 90% of tumor mass. The serine protease fibroblast activation protein (FAP) is overexpressed selectively in CAFs, drawing interest in FAP as a stromal target. The quinoline-based FAP-inhibitor PET tracer, 68Ga-FAPI-04, has been previously shown to yield high tumor-to-background ratios (TBR) in patients with various cancers. Recent developments towards an improved compound for therapeutic application have identified FAPI-46 as a promising agent due to a longer tumor retention time in comparison with FAPI-04. Here we present a PET biodistribution and radiation dosimetry study of 68Ga-FAPI-46 in cancer patients. Methods: Six patients with different cancers underwent serial 68Ga-FAPI-46 PET/CT scans at three time points following radiotracer injection: 10 minutes, 1 hour, and 3 hours. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and body remainder. OLINDA/EXM v.1.1 software was used to fit and integrate the kinetic organ activity data to yield total body and organ time-integrated activity coefficients/residence times and finally organ absorbed doses. Standardized uptake values (SUV) and TBR were generated from the contoured tumor and source organ volumes. Spherical volumes in muscle and blood pool were also obtained for TBR (Tumor SUVmax / Organ SUVmean). Results: At all timepoints, the highest organ SUVmax was observed in the liver. Tumor and organ mean SUVs decreased whereas TBRs in all organs but the uterus increased with time. The highest TBRs at 3 hours were observed with the bone marrow (31.1), muscle (22.8), heart (19.1), and spleen (19.0). Organs with the highest effective doses were the bladder wall (2.41E-03 mSv/MBq), followed by ovaries (1.15E-03 mSv/MBq) and red marrow (8.49E-04mSv/MBq). The average effective total body dose was 7.80E-03 mSv/MBq. Thus for administration of 200 MBq 68Ga-FAPI-46 the effective total body dose is 1.56 mSv ± 0.26 mSv, in addition to approximately 3.7 mSv from one low-dose CT scan done for attenuation correction. Conclusion: 68Ga-FAPI-46 PET/CT has a favorable dosimetry profile with an estimated whole body dose of 5.3 mSv for an administration of 200 MBq (5.4 mCi) of 68Ga-FAPI-46 (1.56± 0.26 mSv from the PET tracer and 3.7 mSv from one low-dose CT scan). The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.