Prediction of gene therapy-induced tumor size changes by the vascularity changes measured using dynamic contrast-enhanced MRI.
We studied the changes of tumor size after gene therapy treatment and its relationship with the changes of vascular volume as measured by dynamic contrast-enhanced magnetic resonance imaging (MRI), to investigate whether the vascular changes is predictive of tumor regression. The study was carried out using a spontaneously regressing rat tumor model (C6 Glioma grown subcutaneously in rats). Three rats were treated with recombinant adenoviruses expressing three genes, mouse interleukin 1-alpha (IL1-alpha), mouse interferon gamma (IFN-gamma), and human transforming growth factor beta (TGF-beta), one from each kind. Two rats were treated with saline as controls. Longitudinal studies were performed to monitor the changes of tumor volume (based on T(2)-weighted images) and the vascular volume (based on dynamic contrast enhanced images). In untreated animals, tumor regression was preceded by several days with a decrease in vascular volume. When the tumor growth was perturbed by expression of mouse IL-1alpha, the increase in vascular volume was correlated with the continuing growth in size, and the decrease in vascular volume was predictive of the onset of tumor regression. As new advances in immunotherapy in cancer treatment emerge, the ability to determine the efficacy of therapy as early as possible will enable optimization of treatment regiments. The vascularity changes measured by dynamic MRI may provide a means to serve for this purpose.
Su
M Y
MY
Health Sciences Research Imaging Center, Irvine Hall 164, University of California, Irvine, CA 92697, USA.
Taylor
J A
JA
Villarreal
L P
LP
Nalcioglu
O
O
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008137:Longitudinal Studies; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism; D017711:Nonlinear Dynamics; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins; D012074:Remission Induction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D019786:Gadolinium DTPA