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

PURPOSE: 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). PROCEDURES: 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. 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 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. 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.

Bowel preparation in MRI for detection of endometriosis: Comparison of the effect of an enema, no additional medication and intravenous butylscopolamine on image quality.

PURPOSE: To compare the effect of three different patient preparation strategies for reducing bowel motion on image quality in pelvic MRI. METHODS: Retrospective study in which 95 consecutive patients undergoing pelvic MRI were subdivided based on preparation type for reduction of bowel motion: group 1 (N = 31) fasted 4 h and applied an enema (Bisacodyl 10 mg); group 2 (N = 32) received no medication; group 3 (N = 32) received intravenous butylscopolamine (Buscopan® 50 mg). Image quality was reviewed by visual assessment of delineation (3-point-scale) of pelvic structures: uterus, adnexa, bladder, rectum, sigmoid, uterosacral ligaments, round ligaments and small bowel. As secondary endpoint the presence of rectal wall edema was evaluated. Interobserver agreement was calculated, as well as relative diagnostic odds ratios (RDOR) for the protocols to provide an outcome in the best delineation category. RESULTS: Interobserver agreement proportions varied from 0.48 to 1.00. The rectum and sigmoid colon respectively have a 5.4 and 2.6 RDOR when butylscopolamine is applied compared to Bisacodyl (P = 0.051; P = 0.008), and a 4.2 and 5.7 times higher RDOR with Bisacodyl preparation compared to no medical preparation (P = 0.006; P < 0.01). Small bowel delineation was significantly better with butylscopolamine compared to Bisacodyl (P = 0.007). There was no significant difference in delineation of the other structures between protocols. There is a significant higher chance of observing rectal wall edema with Bisacodyl compared to the other protocols (both P < 0.001). CONCLUSIONS: Butylscopolamine provides better delineation of the small bowel and rectosigmoid compared to Bisacodyl, which in turn, provides better delineation of the rectosigmoid compared to no medication. Moreover, Bisacodyl causes rectal wall edema in the majority of cases.

The feasibility of quantitative MRI of extra-ocular muscles in myasthenia gravis and Graves' orbitopathy.

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra-ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye-motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2water ) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2water values were determined in 12 HC (aged 22-65 years), 11 MG (aged 28-71 years) and six GO (aged 28-64 years) patients at 7 T using Dixon and multi-echo spin-echo sequences. The EOM were semi-automatically 3D-segmented by two independent observers. MANOVA and t-tests were used to assess differences in FF, T2water and volume of EOM between groups (P < .05). Bland-Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was -0.7% (LoA: ±2.1%) for the different observers; the bias in FF was -0.3% (LoA: ±2.8%) and 0.03 cm3 (LoA: ± 0.36 cm3 ) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm3 ) and MG (0.8 ± 0.2 cm3 ) compared with HC (0.6 ± 0.2 cm3 ). The average T2water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.