Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer

Fluorine-18 3'-deoxy-3'-fluorothymidine ((FLT)-F-18) is a tissue proliferation marker which has been suggested as a new tumour-specific imaging tracer in positron emission tomography (PET). The objectives of this study were to investigate the pharmacokinetics of (FLT)-F-18 in patients with colorectal cancer, defining methodologies for the quantitative analysis of the in vivo (FLT)-F-18 uptake and subsequently assessing the accuracy of semi-quantitative measures. Dynamic acquisitions over a single field of view of interest identified by computed tomography were carried out for up to 60 min following injection of (FLT)-F-18 (360+/-25 MBq). Dynamic arterial blood sampling was carried out in order to provide a blood input function. Simultaneous venous samples were also taken in order to investigate their potential utilisation in deriving a hybrid input function. Arterial and venous blood samples at 5, 15, 30, 60 and 90 min p.i. were used for metabolite analysis. Eleven patients with primary and/or metastatic colorectal cancer were studied on a lesion by lesion basis (n=21). All acquired images were reconstructed using ordered subsets expectation maximisation and segmented attenuation correction. Time-activity curves were derived by image region of interest (ROI) analysis and image-based input functions were obtained using abdominal or thoracic aorta ROIs. Standardised uptake values (SUVs) were calculated to provide semi-quantitative indices of uptake, while non-linear regression (NLR) methodology in association with a three-compartment model and Patlak analysis were carried out to derive the net influx constant K-i. The metabolite analysis revealed two radioactive metabolites, with the parent compound representing similar to80% of the total radioactivity in the 30-min plasma sample. In the case of NLR, better fits were obtained with a 3k model (i.e. k(4)=0) for both lesion and bone marrow time-activity curves. For the same lesions, a high correlation was observed between the K-i derived from either Patlak analysis or NLR(3k) and the corresponding SUVs. Our results also suggest that the quantitative behaviour of (FLT)-F-18 in vivo (up to 60 min p.i.) may be characterised using a 3k model or Patlak analysis in combination with image-derived input functions. The good correlation found between the SUVs (at 60 min) and K-i values supports the use of semi-quantitative indices to assess the proliferation rate of colorectal cancer lesions in vivo with (FLT)-F-18.