In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography
- 1Institute of Nuclear Medicine, and Department of Surgery, Royal Free and University College Medical School, Middlesex Hospital, London, UK
- 2Department of Histopathology, Royal Free and University College Medical School, Middlesex Hospital, London, UK
- 3Institute of Nuclear Medicine, Royal Free and University College Medical School, Middlesex Hospital, London, UK
- 4IRSL Cyclotron Unit, Hammersmith Hospital, London, UK
- 5Department of Surgery, Royal Free and University College Medical School, Middlesex Hospital, London, UK
- Correspondence to:
Institute of Nuclear Medicine, Middlesex Hospital, Mortimer St, London, W1T 3AA, UK;
- Accepted 8 July 2003
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.
- PET, positron emission tomography
- CT, computed tomography
- 18FDG, 18F labelled 2-fluoro-2-deoxy-d-glucose
- 18FLT, 18F labelled 3′-deoxy-3-fluorothymidine
- CRC, colorectal cancer
- TK, thymidine kinase 1
- SUV, standardised uptake value
- ROI, regions of interest
- H&E, haematoxylin and eosin
- TBS, Tris buffered saline
- LI, labelling index