Biodistribution and radiation dosimetry in cancer patients of the ascorbic acid analogue 6-Deoxy-6-[18F] fluoro-L-ascorbic acid PET imaging: first-in-human study

• Published in: European journal of nuclear medicine and molecular imaging Vol. 50; no. 10; pp. 3072 - 3083
• Main Authors: Long, Yali, Yi, Chang, Wu, Renbo, Zhang, Yuying, Zhang, Bing, Shi, Xinchong, Zhang, Xiangsong, Zha, Zhihao
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Acids; Adrenal glands; Animals; Ascorbic acid; Cancer; Cancer research; Cardiology; Choroid plexus; Computed tomography; Dosimeters; Dosimetry; Fluorine isotopes; Human performance; Humans; Imaging; Kidneys; Liver; Localization; Medical imaging; Medical research; Medicine; Medicine & Public Health; Mice; Neoplasms - diagnostic imaging; Nuclear Medicine; Oncology; Original Article; Orthopedics; Patients; Pharmaceuticals; Pituitary; Pituitary gland; Positron emission; Positron Emission Tomography Computed Tomography - methods; Positron-Emission Tomography - methods; Radiation; Radiochemistry; Radioisotopes; Radiology; Radiometry; Tissue Distribution; Tumors; L-ascorbic acid; [; Dosimetry; F]DFA; Biodistribution; PET/CT; [18F]DFA
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-023-06262-9

Purpose Clinical studies on the use of ascorbic acid (AA) have become a hot spot in cancer research. There remains an unmet need to assess AA utilization in normal tissues and tumors. 6-Deoxy-6-[ 18 F]fluoro-L-ascorbic acid ([ 18 F]DFA) displayed distinctive tumor localization and similar distribution as AA in mice. In this study, to evaluate the distribution, tumor detecting ability and radiation dosimetry of [ 18 F]DFA in humans, we performed the first-in-human PET imaging study. Methods Six patients with a variety of cancers underwent whole-body PET/CT scans after injection of 313–634 MBq of [ 18 F]DFA. Five sequential dynamic emission scans in each patient were acquired at 5–60 min. Regions of interest (ROI) were delineated along the edge of the source-organ and tumor on the transverse PET slice. Tumor-to-background ratio (TBR) was obtained using the tumor SUVmax to background SUVmean. Organ residence times were calculated via time-activity curves, and human absorbed doses were estimated from organ residence time using the medical internal radiation dosimetry method. Results [ 18 F]DFA was well tolerated in all subjects without serious adverse event. The high uptake was found in the liver, adrenal glands, kidneys, choroid plexus, and pituitary gland. [ 18 F]DFA accumulated in tumor rapidly and the TBR increased over time. The average SUVmax of [ 18 F]DFA in tumor lesions was 6.94 ± 3.92 (range 1.62–22.85, median 5.94). The organs with the highest absorbed doses were the liver, spleen, adrenal glands, and kidneys. The mean effective dose was estimated to be 1.68 ± 0.36 E −02  mSv/MBq. Conclusions [ 18 F]DFA is safe to be used in humans. It showed a similar distribution pattern as AA, and displayed high uptake and retention in tumors with appropriate kinetics. [ 18 F]DFA might be a promising radiopharmaceutical in identifying tumors with high affinity for SVCT2 and monitoring AA distribution in both normal tissues and tumors. Trial registration Chinese Clinical Trial Registry; Registered Number: ChiCTR2200057842 (registered 19 March 2022).