- December 13, 2019
- Category: Nuclear Medicine, Scientific Publications
Radiation Dosimetry and Biodistribution of 68Ga-FAPI-46 PET Imaging in Cancer Patients
Catherine Meyer1,2, Magnus Dahlbom1,2, Thomas Lindner3, Sebastien Vauclin4, Christine Mona2, Roger Slavik1,2,5, Johannes Czernin2,6,7, Uwe Haberkorn3,7,8, and Jeremie Calais1,2,5,6
1 Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA, Los Angeles, California
2 Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
3 Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
4 DOSIsoft SA, Cachan, France
5 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
6 Institute of Urologic Oncology, UCLA, Los Angeles, California
7 Clinical Cooperation Unit Nuclear Medicine, DKFZ Heidelberg, Heidelberg, Germany
8 Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany
Introduction: Targeting cancer-associated ﬁbroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy because they can constitute as much as 90% of a 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 (FAPI) PET tracer 68Ga-FAPI-04 has been pre-viously shown to yield high tumor-to-background ratios (TBRs) in patients with various cancers. Recent developments toward an im-proved compound for therapeutic application have identiﬁed FAPI-46 as a promising agent because of an increased tumor retention time in comparison with FAPI-04. Here, we present a PET biodis-tribution 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 3 time points after radiotracer injection: 10 min, 1 h, and 3 h. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and re-mainder of body. OLINDA/EXM software, version 1.1, was used to ﬁt and integrate the kinetic organ activity data to yield total-body and organ time-integrated activity coefﬁcients and residence times and, ﬁnally, organ-absorbed doses. SUVs and TBR were generated from the contoured tumor and source-organ volumes. Spheric vol-umes in muscle and blood pool were also obtained for TBR (tumor SUVmax/organ SUVmean).
Results: At all time points, average SUVmax was highest in the liver. Tumor and organ SUVmean decreased over time, whereas TBRs in all organs but the uterus increased. The organs with the highest effective doses were bladder wall (2.41E−03 mSv/MBq), followed by ovaries (1.15E−03 mSv/MBq) and red mar-row (8.49E−04 mSv/MBq). The average effective total-body dose was 7.80E−03 mSv/MBq.
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 1 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.