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First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients

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Abstract

Purpose

This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients.

Methods

The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software.

Results

[18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 μSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases.

Conclusions

We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

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Data availability

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

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Acknowledgements

The authors thank Dr. William Eckelman and Dr. Guochang Wang for advice and suggestions in preparation of this manuscript.

Funding

This study was supported by Guangdong regional joint fund (2022A1515110941); Guangzhou basic and applied basic research (2023A04J1196), Science and Technology Program of Guangzhou (202201020558) and enhancing scientific research in Guangzhou Medical University.

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Author notes

  1. Ruiyue Zhao and Miao Ke contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China

    Ruiyue Zhao, Miao Ke, Jie Lv, Shaoyu Liu, Yuheng Liu, Jing Zhang, Lifu Xu, Lin Zhu & Xinlu Wang

  2. Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, Guangdong, China

    Di Gu, Mingzhao Li, Chao Cai, Yongda Liu & Guohua Zeng

  3. Five Eleven Pharma Inc, 3700 Market St, Philadelphia, PA, 19104, USA

    David Alexoff, Karl Ploessl & Hank F. Kung

  4. College of Chemistry, Beijing Normal University, Beijing, 100875, China

    Lin Zhu

  5. Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Hank F. Kung

Authors
  1. Ruiyue Zhao
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ruiyue Zhao, Miao Ke, Jie Lv, Shaoyu Liu, Yuheng Liu, Jing Zhang, Lifu Xu, Di Gu, Mingzhao Li, Chao Cai, Yongda Liu, Guohua Zeng, David Alexoff, Karl Ploessl, Lin Zhu, Hank F. Kung, and Xinlu Wang. The first draft of the manuscript was written by Ruiyue Zhao, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lin Zhu, Hank F. Kung or Xinlu Wang.

Ethics declarations

Ethical approval

This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (ES-2023-141), and it was conducted in accordance with the principles of the Declaration of Helsinki.

Consent to participate

Informed consent was obtained from all participants included in the study

Conflict of interest

David Alexoff, Karl Ploessl, and Hank F. Kung are employees of Five Eleven Pharma, and Hank Kung is also the found and board of the company, which holds the patent rights for [18F]AlF-P16-093 and related technology. Other authors have no conflicts of interest or relevant financial activities to disclose.

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Zhao, R., Ke, M., Lv, J. et al. First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients. Eur J Nucl Med Mol Imaging 51, 1753–1762 (2024). https://doi.org/10.1007/s00259-024-06596-y

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