In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography.
BACKGROUND
and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC).


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 (18)FLT 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 (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT 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 (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4).


CONCLUSIONS
(18)FLT 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.
Institute of Nuclear Medicine, University College Medical School, Middlesex Hospital, London, UK. daren.francis@ucl.ac.uk
D L
DL
Francis
A
A
Freeman
D
D
Visvikis
D C
DC
Costa
S K
SK
Luthra
M
M
Novelli
I
I
Taylor
P J
PJ
Ell
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002430:Cecal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D014055:Tomography, Emission-Computed / Q000379:methods*