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

Yali Long; Chang Yi; Renbo Wu; Yuying Zhang; Bing Zhang; Xinchong Shi; Xiangsong Zhang; Zhihao Zha

doi:10.1007/s00259-023-06262-9

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

Eur J Nucl Med Mol Imaging. 2023 Aug;50(10):3072-3083. doi: 10.1007/s00259-023-06262-9. Epub 2023 May 16.

Authors

Yali Long¹, Chang Yi¹, Renbo Wu¹, Yuying Zhang¹, Bing Zhang¹, Xinchong Shi¹, Xiangsong Zhang², Zhihao Zha³

Affiliations

¹ Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58# Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
² Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58# Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China. zhxiangs@mail.sysu.edu.cn.
³ Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58# Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, People's Republic of China. zhazhh@mail.sysu.edu.cn.

PMID: 37191679
DOI: 10.1007/s00259-023-06262-9

Abstract

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-[¹⁸F]fluoro-L-ascorbic acid ([¹⁸F]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 [¹⁸F]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 [¹⁸F]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: [¹⁸F]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. [¹⁸F]DFA accumulated in tumor rapidly and the TBR increased over time. The average SUVmax of [¹⁸F]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: [¹⁸F]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. [¹⁸F]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).

Keywords: Biodistribution; Dosimetry; L-ascorbic acid; PET/CT; [18F]DFA.

MeSH terms

Animals
Humans
Mice
Neoplasms* / diagnostic imaging
Positron Emission Tomography Computed Tomography* / methods
Positron-Emission Tomography / methods
Radiometry
Tissue Distribution

Abstract

MeSH terms

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