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Determining the optimal pharmacokinetic modelling and simplified quantification method of [18F]AlF-P16-093 for patients with primary prostate cancer (PPCa)

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Abstract

Purpose

This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer.

Methods

Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis.

Results

In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28–34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01).

Conclusions

This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution.

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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

The authors thank Dr. William Eckelman for his advice and suggestions in the 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), enhancing scientific research at Guangzhou Medical University, Scientific Instrument Innovation Team of the Chinese Academy of Sciences (GJJSTD20180002), the Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province (2023B1212060052), Shenzhen Science and Technology Innovation Committee (20220531100209020), and the Department of Science and Technology of Guangdong Province (2022A1515110716).

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Author notes

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

Authors and Affiliations

  1. Department of Nuclear Medicine, The Key Laboratory of Advanced Interdisciplinary Studies Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China

    Ruiyue Zhao, Miao Ke, Jie Lv, Huizhen Zhong, Yulu He, Lin Zhu & Xinlu Wang

  2. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China

    Zeheng Xia & Tao Sun

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

    Di Gu, Yongda Liu & Guohua Zeng

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

    Lin Zhu

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

    David Alexoff & Hank F. Kung

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

    Hank F. Kung

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  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 RZ, ZX, MK, JL, HZ, YH, DG, YL, GZ, LZ, DA, HF.K, XW, and TS. The first draft of the manuscript was written by RZ and ZX, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xinlu Wang or Tao Sun.

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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 and Hank F. Kung are employees of Five Eleven Pharma, and Hank Kung is also the founder 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., Xia, Z., Ke, M. et al. Determining the optimal pharmacokinetic modelling and simplified quantification method of [18F]AlF-P16-093 for patients with primary prostate cancer (PPCa). Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06624-x

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