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

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 (V_b). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (V_t) 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, V_b, and V_t 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 V_t values (R² = 0.949, P < 0.01). Both V_t 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.

Keywords: Dynamic PET; PSMA; Pharmacokinetic modelling; Primary prostate cancer; [18F]AlF-P16-093.