RT Journal Article
SR Electronic
T1 Evaluation of tumor response to the antivascular agent DMXAA using 18F-FMISO PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 451
OP 451
VO 50
IS supplement 2
A1 Oehler-Janne, Christoph
A1 O'Donoghue, Joseph
A1 Ling, C.Clifton
A1 Carlin, Sean
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/451.abstract
AB 451 Objectives To evaluate 18F-FMISO PET in assessing tumor response to the antivascular compound 5,6-dimethylxanthenone (DMXAA). Methods Mice bearing HT29 tumor xenografts were co-administered 1mCi 18F-FMISO and 1.5 mg pimonidazole (PIMO) i.v. MicroPET images were obtained 60-90 minutes post-administration. Animals were then administered 20 mg/kg DMXAA or vehicle-only. 24h later, animals were co-administered 1 mCi 18F-FMISO and 0.6 mg EF5 i.v. and MicroPET images obtained as before. Hoechst 33342 (1 mg i.v.) was then administered. Following sacrifice, tumors were removed and 10 μm-thick cryosections obtained for immunofluorescence visualization of PIMO, EF5 and Hoechst 33342. Paired 18F-FMISO images (pre- and post-DMXAA) were analyzed and compared with immunofluorescence data. Results Of 12 tumors from DMXAA-treated animals, 5 showed marked reductions in 18F-FMISO SUV and 7 did not. Assessment of the distributions of PIMO (pre-DMXAA) and EF5 (post-DMXAA) produced similar results. In tumors where 18F-FMISO SUV decreased, the degree of reduction correlated with the difference between PIMO- and EF5-positive tumor fractions (r2~0.5). These tumors also showed a reduced level of blood perfusion as assessed by Hoechst 33342 staining. No significant differences were observed in either control tumors or in treated tumors that showed no reduction in 18F-FMISO SUV. Conclusions A heterogeneous response to DMXAA was observed. Our data suggest that a reduction in 18F-FMISO SUV following treatment most likely indicates a reduction in blood perfusion, and thus hypoxia tracer supply, rather than a reduction in tumor hypoxia. Further studies will evaluate if 18F-FMISO PET has utility as an indicator of treatment outcome.