Chad Haney PhD, Presenter: Nothing to Disclose

Adrian Parasca BA, Abstract Co-Author: Nothing to Disclose

Rebecca Bell BS, Abstract Co-Author: Nothing to Disclose

Marta A. Zamora BS, Abstract Co-Author: Nothing to Disclose

Xiaobing Fan PhD, Abstract Co-Author: Nothing to Disclose

Gregory Stanislaus Karczmar PhD, Abstract Co-Author: Nothing to Disclose

Helena Mauceri PhD, Abstract Co-Author: Nothing to Disclose

Ralph Weichselbaum MD, Abstract Co-Author: Stockholder, GenVec, Inc

Howard Halpern MD, PhD, Abstract Co-Author: Nothing to Disclose

Charles A. Pelizzari PhD, Abstract Co-Author: Research grant, Varian Medical Systems, Inc

et al, Abstract Co-Author: Nothing to Disclose

Here we report the use of multi-modality, non-invasive imaging for early analysis of spatial patterns of tumor response to combined radiation and antivascular gene therapy. Changes of vascular perfusion using MRI and tissue oxygenation measurements using electron paramagnetic resonance imaging (EPRI) were registered to characterize a “signature” for response.

Nude mice were inoculated with PC-3 xenografts in the right hind limb. On the initial treatment day, both EPRI and MRI imaging were performed, followed by injection of the vector, and irradiation with X-ray to 10 Gy. A null vector without radiation was used as a control . Three days later, the mice were again imaged with EPRI and MRI. No additional doses of either viral vector or radiation were given after day 0. T2 weighted spin echo was used for image registration and anatomical guidance. 4D spectral-spatial images from EPRI were used to map the pO2.

Using manual image registration, we correlated the EPRI-derived oxymetric measurements with the MRI perfusion images. Oxygen increased significantly in all ROIs in all mice receiving TNFα + 10 Gy compared to null vector alone (p < 0.025). The rim of the tumor had an increase oxygen of 19 mm Hg relative to day 0 (p = 0.04). The tumors in the control mice did not have a significant change in pO2 after null vector treatment. The contrast uptake rate was lower in the cores of tumors after full treatment compared to controls (p = 0.01). The null vector treated tumors’ cores had an increase in the contrast uptake rate compared to day 0 (p = 0.03). The overall contrast agent washout rate was higher in the rims of the treated tumors when compared controls (p = 0.029).

This is the first report of quantitative, absolute oxygen measurements being correlated with tissue perfusion, in vivo and non-invasively. Image registration facilitated interpretation of the functional images aided by the higher resolution anatomical image. Radiation mediated antivascular therapy significantly improves tissue oxygenation. The change in oxygenation is associated with a change in the pattern of perfusion; contrast media uptake rate decreases and washout rate increases.

The radiation-induced gene therapy used here is currently undergoing clinical trials. DCE-MRI could be used to guide subsequent fractions in an adaptive image guided approach.

Haney, C, Parasca, A, Bell, R, Zamora, M, Fan, X, Karczmar, G, Mauceri, H, Weichselbaum, R, Halpern, H, Pelizzari, C, et al, , Assessment of Radiation Mediated Gene Therapy via Multimodality Imaging.  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6017160.html