Molecular imaging with ¹⁸F-FDG PET has been proven useful in the management of colorectal cancer. ¹⁸F-FDG PET plays a pivotal role in staging before surgical resection of recurrent colorectal cancer and metastases, in the localization of recurrence in patients with an unexplained rise in serum carcinoembryonic antigen levels, and in the assessment of residual masses after treatment. Currently, there is increasing interest in the role of ¹⁸F-FDG PET beyond staging. The technique appears to have significant potential for the characterization of tumors and for the prediction of prognosis in the context of treatment stratification and early assessment of tumor response to therapy. This systematic review provides an overview of the literature on the value of ¹⁸F-FDG PET for monitoring and predicting the response to therapy in colorectal cancer. The review covers chemotherapy response monitoring in advanced colorectal cancer, monitoring of the effects of local ablative therapies, and preoperative radiotherapy and multimodality treatment response evaluation in primary rectal cancer. Given the added value of ¹⁸F-FDG PET for these indications, implementation in clinical practice and systematic inclusion in therapeutic trials to exploit the potential of ¹⁸F-FDG PET are warranted.

Biological behavior of cancer cells is not only determined by the genotype of the tumor cells, but is also modified by the tumor microenvironment. For example, hypoxia, which is the result of an insufficient tumor microvasculature, plays a major role in cancer biology. Hypoxia is associated with more aggressive tumor behavior, impaired response to radiotherapy and chemotherapy, and worse clinical outcome.¹ x 1 Rademakers, SE, Span, PN, Kaanders, JH, Sweep, FC, van der Kogel, AJ, and Bussink, J. Molecular aspects of tumour hypoxia. Mol Oncol. 2008; 2: 41–53 Abstract | Full Text | Full Text PDF | PubMed | Scopus (93) | Google Scholar See all References The metabolism of carcinomas is affected by hypoxia, as tumor cells switch to anaerobic glycolysis with the production of lactate under hypoxic conditions (Pasteur effect). However, in cancer cells, a high glycolytic rate is also observed in the presence of oxygen (Warburg effect). This glycolytic tumor metabolism is associated with selective growth advantage, tumor cell survival and treatment resistance.² x 2 Busk, M, Horsman, MR, Jakobsen, S, Bussink, J, van der Kogel, A, and Overgaard, J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging. 2008; 35: 2294–2303 Crossref | PubMed | Scopus (74) | Google Scholar See all References ^{, 3} x 3 Ganapathy, V, Thangaraju, M, and Prasad, PD. Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther. 2009; 121: 29–40 Crossref | PubMed | Scopus (369) | Google Scholar See all References ^{, 4} x 4 Meijer, TW, Kaanders, JH, Span, PN, and Bussink, J. Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res. 2012; 18: 5585–5594 Crossref | PubMed | Scopus (185) | Google Scholar See all References The higher rate of glucose consumption is one of the reasons why 18-fluoro-2-deoxyglucose positron emission tomography (¹⁸FDG-PET) is useful as an imaging tool in solid tumors.² x 2 Busk, M, Horsman, MR, Jakobsen, S, Bussink, J, van der Kogel, A, and Overgaard, J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging. 2008; 35: 2294–2303 Crossref | PubMed | Scopus (74) | Google Scholar See all References ,⁵ x 5 Gillies, RJ, Robey, I, and Gatenby, RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med. 2008; 49: 24S–42S Crossref | PubMed | Scopus (360) | Google Scholar See all References ,⁶ x 6 Plathow, C and Weber, WA. Tumor cell metabolism imaging. J Nucl Med. 2008; 49: 43S–63S Crossref | PubMed | Scopus (206) | Google Scholar See all References

Purpose This review aims to provide insight into the factors that influence quantification of glucose metabolism by FDG PET images in oncology as well as their influence on repeated measures studies (i.e. treatment response assessment), offering improved understanding both for clinical practice and research. Methods Structural PubMed searches have been performed for the many factors affecting quantification of glucose metabolism by FDG PET. Review articles and references lists have been used to supplement the search findings. Results Biological factors such as fasting blood glucose level, FDG uptake period, FDG distribution and clearance, patient motion (breathing) and patient discomfort (stress) all influence quantification. Acquisition parameters should be adjusted to maximize the signal to noise ratio without exposing the patient to a higher than strictly necessary radiation dose. This is especially challenging in pharmacokinetic analysis, where the temporal resolution is of significant importance. The literature is reviewed on the influence of attenuation correction on parameters for glucose metabolism, the effect of motion, metal artefacts and contrast agents on quantification of CT attenuation-corrected images. Reconstruction settings (analytical versus iterative reconstruction, post-reconstruction filtering and image matrix size) all potentially influence quantification due to artefacts, noise levels and lesion size dependency. Many region of interest definitions are available, but increased complexity does not necessarily result in improved performance. Different methods for the quantification of the tissue of interest can introduce systematic and random inaccuracy. Conclusions This review provides an up-to-date overview of the many factors that influence quantification of glucose metabolism by FDG PET.