# Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients

## TL;DR

This study explores the challenges of using a specific PET/CT radiotracer to image ovarian cancer patients, highlighting difficulties in pharmacokinetic modeling due to anatomical and physiological factors.

## Contribution

The paper identifies and discusses practical challenges in pharmacokinetic modeling of [18F]fluoro-PEG-folate in ovarian cancer patients.

## Key findings

- Only four out of 22 tumor lesions were suitable for pharmacokinetic modeling due to tracer uptake and anatomical challenges.
- The irreversible 2T3k model showed the best fit for pharmacokinetic analysis of the tracer in the studied lesions.
- All 22 lesions were positive for folate receptor alpha (FRα) based on immunohistochemical staining.

## Abstract

To describe the pharmacokinetic properties of the [18F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).

In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d’Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [18F]fluoro-PEG6-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.

The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [18F]fluoro-PEG6-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.

Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.

The online version contains supplementary material available at 10.1007/s11307-024-01922-0.