Small-animal PET/CT for monitoring the development and response to chemotherapy of thymic lymphoma in Trp53-/- mice.
Transgenic mouse models of human cancers represent one of the most promising approaches to elucidate clinically relevant mechanisms of action and provide insights into the treatment efficacy of new antitumor drugs. The use of Trp53 transgenic mice (Trp53 knockout [Trp53(-/-)] mice) for these kinds of studies is, so far, restricted by limitations in detecting developing tumors and the lack of noninvasive tools for monitoring tumor growth, progression, and treatment response.


METHODS
We hypothesized that quantitative small-animal PET with (18)F-FDG was able to detect the onset and location of tumor development, follow tumor progression, and monitor response to chemotherapy. To test these hypotheses, C57BL/6J Trp53(-/-) mice underwent longitudinal small-animal PET during lymphoma development and gemcitabine treatment. Trp53 wild-type (Trp53(+/+)) mice were used as controls, and histology after full necropsy served as the gold standard.


RESULTS
In Trp53(+/+) mice, the thymic standardized uptake value (SUV) did not exceed 1.0 g/mL, with decreasing (18)F-FDG uptake over time. Conversely, all Trp53(-/-) mice that developed thymic lymphoma showed increasing thymic glucose metabolism, with a mean SUV doubling time of 9.0 wk (range, 6.0-17.5 wk). Using an SUV of 3.0 g/mL as a criterion provided a sensitivity of 78% and a specificity of 100% for the detection of thymic lymphoma. Treatment monitoring with (18)F-FDG PET correctly identified all histologic responses and relapses to gemcitabine.


CONCLUSIONS
(18)F-FDG small-animal PET can be used to visualize onset and progression of thymic lymphomas in Trp53(-/-) mice and monitor response to chemotherapy. Thus, (18)F-FDG small-animal PET provides an in vivo means to assess intervention studies in the Trp53 transgenic mouse model.
Walter
Martin A
MA
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California, USA. m.a.walter@gmx.net
Hildebrandt
Isabel J
IJ
Hacke
Katrin
K
Kesner
Adam L
AL
Kelly
Owen
O
Lawson
Gregory W
GW
Phelps
Michael E
ME
Czernin
Johannes
J
Weber
Wolfgang A
WA
Schiestl
Robert H
RH
D000375:Aging / Q000502:physiology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18; D007091:Image Processing, Computer-Assisted; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008940:Mitotic Index; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D014055:Tomography, Emission-Computed; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D019788:Fluorodeoxyglucose F18; D000093542:Gemcitabine