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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

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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).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We extend our profound appreciation to Professor Ganghua Tang for his generous contribution of the S value tables and the volunteers who participated in the imaging study.

Funding

This study was supported by the Natural Science Foundation of Guangdong province (no. 2022A1515011670) and the Key Research and Development Program of Guangzhou City (no. 202206010046).

Author information

Author notes

  1. Yali Long, Chang Yi, and Renbo Wu contributed equally to this work.

Authors and 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

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

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  1. Yali Long
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  2. Chang Yi
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  7. Xiangsong Zhang
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  8. Zhihao Zha
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Contributions

All authors contributed to the study conception and design. YLL participated in the design of the study, collected the patients’ data, and drafted the manuscript. CY and RBW performed the material preparation, data collection, and analysis. YYZ, BZ, and XCS processed the figures and performed a critical revision of the manuscript. ZHZ and XSZ conceived and designed the study and supervised the project. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Xiangsong Zhang or Zhihao Zha.

Ethics declarations

Ethics approval

The current study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of Sun Yat-Sen University (The ethical approval number is [2021]751-1).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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The authors affirm that all individual participants provided informed consent for anonymised evaluation and publication of their data.

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The authors declare no competing interests.

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Long, Y., Yi, C., Wu, R. et al. 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 50, 3072–3083 (2023). https://doi.org/10.1007/s00259-023-06262-9

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