Abstract

Background and aims: Positron emission tomography (PET) using ¹⁸F labelled 2-fluoro-2-deoxy-D-glucose (¹⁸FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3′-deoxy-3-fluorothymidine (¹⁸FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of ¹⁸FLT and ¹⁸FDG 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 ¹⁸FDG and ¹⁸FLT 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 ¹⁸FLT and ¹⁸FDG. Three of the five resected liver metastases were also avid for ¹⁸FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of ¹⁸FLT 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 ¹⁸FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with ¹⁸FDG avid lesions (r =0.4).

Conclusions:¹⁸FLT 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.