Non-invasive evaluation of tumour hypoxia in the Shionogi tumour model for prostate cancer with 18F-EF5 and positron emission tomography.
OBJECTIVE
To evaluate hypoxia non-invasively in androgen-dependent (AD), regressing (6-days after castration, RG) and androgen-independent (AI) Shionogi tumours, using the radiolabelled tracer for hypoxia, 18F-EF5, and positron emission tomography (PET).


METHODS
Groups of mice bearing AD, RG and AI Shionogi tumours were co-injected with 18F-EF5 and unlabelled EF5. The mice were imaged non-invasively with PET to examine the accumulation of 18F-EF5 in hypoxic regions of the tumour. The tumours were subsequently placed in a gamma-counter, or disaggregated for flow cytometry, to determine the levels of 18F-EF5 and the percentage of hypoxic cells present in the tumour, respectively.


RESULTS
The mean (sd) levels of hypoxia in AD Shionogi tumours decreased significantly 6 days after androgen ablation as measured by flow cytometry, from 17.1 (4.77) to 1.74 (0.46)% (P=0.003). There were no significant differences in the levels of 18F-EF5 in the tissue between AD and RG tumours using region-of-interest analysis of PET images or gamma-counting, although the differences were significant when measured by flow cytometry. However, mean (sd) levels of hypoxia in AI Shionogi tumours were significantly higher than in AD tumours regardless of the analysis method; PET, 10.5 (4.93)x10(-5)) Bq/cm2 (P=0.017), flow cytometry, 42.98 (3.35)% (P<0.001), well count, 6.81 (1.17)x10(4) and 13.1 (1.99)x10(4) cpm/g, for AD and AI tumours, respectively (P<0.001).


CONCLUSIONS
Differences in hypoxia between AD and AI, but not RG, Shionogi tumours can be detected non-invasively with 18F-EF5 and PET. As prostate tumours are hypoxic and the oxygen levels can change with androgen ablation, noninvasive imaging of hypoxia with PET and 18F-EF5 might ultimately have a prognostic and/or diagnostic role in the clinical management of the disease.
Yapp
Donald T T
DT
The Department of Advanced Therapeutics, BC Cancer Agency, Vancouver, Canada. dyapp@bccrc.ca
Woo
Janet
J
Kartono
Aileen
A
Sy
Jonathan
J
Oliver
Thomas
T
Skov
Kirsten A
KA
Koch
Cameron J
CJ
Adomat
Hans
H
Dragowska
Wieslawa H
WH
Fazli
Ladan
L
Fadzli
Ladan
L
Ruth
Thomas
T
Adam
Michael J
MJ
Green
David
D
Gleave
Martin
M
D000726:Androgen Antagonists / Q000008:administration & dosage; D000728:Androgens / Q000378:metabolism; D000818:Animals; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity
D000726:Androgen Antagonists; D000728:Androgens; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D010100:Oxygen