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@article{Heinzmann:2018:10.2967/jnumed.117.206250,
author = {Heinzmann, K and Schelhaas, S and Wachsmuth, L and Hermann, S and Rieder, N and Heller, A and Honess, D and Smith, D-M and Fricke, I and Just, N and Doblas, S and Sinkus, R and Doering, C and Schaefers, K and Griffiths, J and Faber, C and Schneider, R and Aboagye, E and Jacobs, A},
doi = {10.2967/jnumed.117.206250},
journal = {Journal of Nuclear Medicine},
pages = {1063--1069},
title = {Thymidine metabolism as confounding factor of 3’-Deoxy-3’-[18F]Fluorothymidine uptake after therapy in a colorectal cancer model},
url = {http://dx.doi.org/10.2967/jnumed.117.206250},
volume = {59},
year = {2018}
}

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TY  - JOUR
AB  - Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT), which was accompanied by increases in markers for proliferation (Ki67, TK1) and for activated DNA damage response (DDR; γH2AX), whereas the effect on cell death was minimal. As tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrate that [18F]FLT PET can non-invasively monitor molecular alterations induced by a cancer treatment, including thymidine metabolism and DDR. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements.
AU  - Heinzmann,K
AU  - Schelhaas,S
AU  - Wachsmuth,L
AU  - Hermann,S
AU  - Rieder,N
AU  - Heller,A
AU  - Honess,D
AU  - Smith,D-M
AU  - Fricke,I
AU  - Just,N
AU  - Doblas,S
AU  - Sinkus,R
AU  - Doering,C
AU  - Schaefers,K
AU  - Griffiths,J
AU  - Faber,C
AU  - Schneider,R
AU  - Aboagye,E
AU  - Jacobs,A
DO  - 10.2967/jnumed.117.206250
EP  - 1069
PY  - 2018///
SN  - 1535-5667
SP  - 1063
TI  - Thymidine metabolism as confounding factor of 3’-Deoxy-3’-[18F]Fluorothymidine uptake after therapy in a colorectal cancer model
T2  - Journal of Nuclear Medicine
UR  - http://dx.doi.org/10.2967/jnumed.117.206250
UR  - http://hdl.handle.net/10044/1/60805
VL  - 59
ER  -

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