Evaluation of treatment-associated inflammatory response on diffusion-weighted magnetic resonance imaging and 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography imaging biomarkers.
OBJECTIVE
Functional imaging biomarkers of cancer treatment response offer the potential for early determination of outcome through the assessment of biochemical, physiologic, and microenvironmental readouts. Cell death may result in an immunologic response, thus complicating the interpretation of biomarker readouts. This study evaluated the temporal effect of treatment-associated inflammatory activity on diffusion magnetic resonance imaging and 2-[(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography imaging (FDG-PET) biomarkers to delineate the effects of the inflammatory response on imaging readouts.


METHODS
Rats with intracerebral 9L gliosarcomas were separated into four groups consisting of control, an immunosuppressive agent dexamethasone (Dex), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and BCNU+Dex. Animals were imaged using diffusion-weighted magnetic resonance imaging and FDG-PET at 0, 3, and 7 days posttreatment.


RESULTS
In the BCNU- and BCNU+Dex-treated animal groups, diffusion values increased progressively over the 7-day study period to approximately 23% over baseline. The FDG percentage change of standard uptake value decreased at day 3 (-30.9%) but increased over baseline levels at day 7 (+20.1%). FDG-PET of BCNU+Dex-treated animals were found to have percentage of standard uptake value reductions of -31.4% and -24.7% at days 3 and 7, respectively, following treatment. Activated macrophages were observed on day 7 in the BCNU treatment group with much fewer found in the BCNU+Dex group.


CONCLUSIONS
Results revealed that treatment-associated inflammatory response following tumor therapy resulted in the accentuation of tumor diffusion response along with a corresponding increase in tumor FDG uptake due to the presence of glucose-consuming activated macrophages. The dynamics and magnitude of potential inflammatory response should be considered when interpreting imaging biomarker results.
Center for Molecular Imaging and Departments of Radiology, University of Michigan, School of Medicine, Ann Arbor, Michigan 48109-0220, USA.
Craig J
CJ
Galbán
Mahaveer S
MS
Bhojani
Kuei C
KC
Lee
Charles R
CR
Meyer
Marcian E
ME
Van Dort
Kyle K
KK
Kuszpit
Robert A
RA
Koeppe
Rajesh
R
Ranga
Bradford A
BA
Moffat
Timothy D
TD
Johnson
Thomas L
TL
Chenevert
Alnawaz
A
Rehemtulla
Brian D
BD
Ross
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002330:Carmustine / Q000009:adverse effects; D003907:Dexamethasone / Q000009:adverse effects; D038524:Diffusion Magnetic Resonance Imaging; D019788:Fluorodeoxyglucose F18; D018316:Gliosarcoma / Q000188:drug therapy / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D003907:Dexamethasone; D002330:Carmustine