In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography

Background and aims: Positron emission tomography (PET) using F-18 labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [F-18] 3'-deoxy-3-fluorothymidine ((FLT)-F-18) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (FLT)-F-18 and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). Patients and methods: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (FLT)-F-18 PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). Results: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (FLT)-F-18 and (18)FDG. Three of the five resected liver metastases were also avid for (FLT)-F-18 and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (FLT)-F-18 had correspondingly very low proliferation. There was a statistically significant positive correlation (r = 0.8, p < 0.01) between SUVs of the tumours visualised with (FLT)-F-18 and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r = 0.4). Conclusions: (FLT)-F-18 PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.