[18F]Fluoromisonidazole PET in rectal cancer

Background: There is an increasing interest in developing predictive biomarkers of tissue hypoxia using functional imaging for personalised radiotherapy in patients with rectal cancer that are considered for neoadjuvant chemoradiotherapy (CRT). The study explores [F-18] fluoromisonidazole ([F-18] FMISO) positron emission tomography (PET) scans for predicting clinical response in rectal cancer patients receiving neoadjuvant CRT. Methods: Patients with biopsy-proven rectal adenocarcinoma were imaged at 0-45min, 2 and 4 h, at baseline and after 8-10 fractions of CRT (week 2). The first 6 patients did not receive an enema (the non-enema group) and the last 4 patients received an enema before PET-CT scan (the enema group). [F-18] FMISO production failed on 2 occasions. Static PET images at 4 h were analysed using tumour-to-muscle (T:M) SUVmax and tumour-to-blood (T:B) SUVmax. The 0-45 min dynamic PET scans were analysed using Casciari model to report hypoxia and perfusion. Akaike information criteria (AIC) were used to compare data fittings for different pharmacokinetic models. Pathological tumour regression grade was scored using American Joint Committee on Cancer (AJCC) 7.0. Shapiro-Wilk test was used to evaluate the normality of the data. Results: Five out of eleven (5/11) patients were classed as good responders (AJCC 0/1 or good clinical response) and 6/11 as poor responders (AJCC 2/3 or poor clinical response). The median T: M SUVmax was 2.14 (IQR 0.58) at baseline and 1.30 (IQR 0.19) at week 2, and the corresponding median tumour hypoxia volume was 1.08 (IQR 1. 31) cm(3) and 0 (IQR 0.15) cm(3), respectively. The median T: B SUVmax was 2.46 (IQR 1.50) at baseline and 1.61 (IQR 0.14) at week 2, and the corresponding median tumour hypoxia volume was 5.68 (IQR 5.86) cm(3) and 0.76 (IQR 0.78) cm(3), respectively. For 0-45 min tumour modelling, the median hypoxia was 0.92 (IQR 0.41) min(-1) at baseline and 0.70 (IQR 0.10) min(-1) at week 2. The median perfusion was 4.10 (IQR 1.71) ml g(-1) min(-1) at baseline and 2.48 (IQR 3.62) ml g(-1) min(-1) at week 2. In 9/11 patients with both PET scans, tumour perfusion decreased in non-responders and increased in responders except in one patient. None of the changes in other PET parameters showed any clear trend with clinical outcome. Conclusions: This pilot study with small number of datasets revealed significant challenges in delivery and interpretation of [F-18] FMISO PET scans of rectal cancer. There are two principal problems namely spill-in from nontumour tracer activity from rectal and bladder contents. Emphasis should be made on reducing spill-in effects from the bladder to improve data quality. This preliminary study has shown fundamental difficulties in the interpretation of [F-18] FMISO PET scans for rectal cancer, limiting its clinical applicability.