Purpose To describe the pharmacokinetic properties of the [ 18F]fuoro-polyethylene glycol(PEG)-folate radiotracer in PET/ CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).... Show morePurpose To describe the pharmacokinetic properties of the [ 18F]fuoro-polyethylene glycol(PEG)-folate radiotracer in PET/ CT imaging of patients with advanced stage epithelial ovarian cancer (EOC). Procedures In fve 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]fuoro-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 diferent models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of ft with the time activity curves by means of the Akaike information criterion. Results The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in fve 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]fuoro-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. Conclusion 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. Show less
In epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide... Show moreIn epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide surgeons to detect metastases otherwise not visible to the naked eye. Previously, we identified 29% more metastatic lesions during cytoreductive surgery using OTL-38, a fluorescent tracer targeting folate receptor-α (FRα). Unfortunately, eleven out of thirteen fluorescent lymph nodes were tumor negative. The current study evaluates the suitability of five biomarkers (EGFR, VEGF-A, L1CAM, integrin αvβ6 and EpCAM) as alternative targets for molecular imaging of EOC metastases and included FRα as a reference. Immunohistochemistry was performed on paraffin-embedded tissue sections of primary ovarian tumors, omental, peritoneal and lymph node metastases from 84 EOC patients. Tumor-negative tissue specimens from these patients were included as controls. EGFR, VEGF-A and L1CAM were highly expressed in tumor-negative tissue, whereas αvβ6 showed heterogeneous expression in metastases. The expression of EpCAM was most comparable to FRα in metastatic lesions and completely absent in the lymph nodes that were false-positively illuminated with OTL-38 in our previous study. Hence, EpCAM seems to be a promising novel target for intraoperative imaging and may contribute to a more reliable detection of true metastatic EOC lesions. Show less
Autotransplantation of ovarian tissue can be used to restore fertility in cancer patients following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor... Show moreAutotransplantation of ovarian tissue can be used to restore fertility in cancer patients following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor detection methods (e.g. PCR analysis, immunohistochemistry) render the ovarian tissue unsuitable for transplantation. As a result, the current tumor detection approach includes assessment of only one or two cortical ovarian fragments that are not transplanted, whereas cortical ovarian tissue fragments that are placed back remain unchecked. The studies described in this thesis focused on determining the risk of reintroducing malignant tumor cells following ovarian tissue autotransplantation using the current tumor detection approach, and novel detection methods by which metastatic disease can be detected in the cortical ovarian fragments that are actually transplanted. These novel detection methods include near-infrared fluorescence (NIRF) imaging, a noninvasive imaging technique by which tumor cells can be specifically illuminated using tumor-targeting probes in the near-infrared range (λ = 700-900 nm), and full field optical coherence tomography, an imaging modality that rapidly produces high-resolution histology-like images without the need to fix, freeze, or stain the tissue. Show less
Peters, I.T.A.; Steen, M.A. van der; Huisman, B.W.; Hilders, C.G.J.M.; Smit, V.T.H.B.M.; Vahrmeijer, A.L.; ... ; Kuppen, P.J.K. 2017
