Bihong T. Chen MD, PhD, Presenter: Nothing to Disclose

Jana Portnow MD, Abstract Co-Author: Nothing to Disclose

Behnam Badie MD, Abstract Co-Author: Nothing to Disclose

Naira Muradyan PhD, Abstract Co-Author: Employee, iCAD, Inc

Karen Aboody PhD, Abstract Co-Author: Nothing to Disclose

Julie Ann Ressler MD, Abstract Co-Author: Nothing to Disclose

Mark S. Shiroishi MD, Abstract Co-Author: Nothing to Disclose

Meng Law MD, Abstract Co-Author: Nothing to Disclose

The purpose of this study is to analyze changes in brain permeability and perfusion following intracerebral injection of neural stem cells and chemotherapy with 5-FC.

Serial brain MRI with DCE and DSC sequences were obtained in patients in this first human NSCs clinical trial. DCE data were processed with iCAD software. This is a pilot feasibility study of oral 5-FC and genetically-modified neural stem cells expressing E.Coli cytosine deaminase for treatment of recurrent high-grade gliomas. HB1.F3.CD neural stem cells expressing E.coli cytosine deaminase were injected into the surgical cavity at the time of debulking craniotomy. On postoperative day 4-10, oral 5-FC was administered to the patients. The anti-tumor response with neural stem cells (NSC) and 5-Fluorocytosine (5-FC) for glioma is dependent on conversion of oral prodrug (5-FC) to active form 5-Fluorouracil (5-FU) by neural stem cells. The concentration and homing of 5-FC to the tumor site may be affected by alteration in brain microvasculature.

Three of the approved 18 patients have been treated and examined. Ktrans values for the first patient in the order of preop, postop day#1 and day#5 are 0.048, 0.029, and 0.018 [1/min]. Ktrans values for the second and third patient in the order of preop, post day#1, #5, and #32 are 0.162, 0.248, 0.365, 0.207, and 0.022, 0.022, 0.055 and 0.024 [1/min]. There is increase in Ktrans values on postop day#5 for both patient #2 and #3. The Ktrans values return to baseline on postop day#32. Other DCE parameters such as Ve, Vp, iAUGC, T10 and ADC show similar changes. rCBV values from DSC sequence for the first patient in the order of preop, postop day#1 and #5 are as follows: 5.06, 2.06, and 5.30. rCBV values for the second patient in the order of preop, postop day#1, #5, #32 are 3.39, 2.23, 3.13 and 4.18. The rCBV values are increased on postop day#5 as compared to the new baseline postop day#1 values.

The results suggest optimal timing of chemotherapy with 5-FC at postop day #5 when high permeability favors delivery of prodrug 5-FC to neural stem cells in glioma.  We believe both neural stem cells and 5-FC contribute to changes in brain microvasculature in gliomas treatment.

MRI brain permeability and perfusion analysis helps to guide and monitor treatment planning and  response in this novel chemotherapeutic protocol with 5-FC and neural stem cells. 

Chen, B, Portnow, J, Badie, B, Muradyan, N, Aboody, K, Ressler, J, Shiroishi, M, Law, M, MRI Brain DCE and DSC Characteristics in a Novel Chemotherapy Using Neural Stem Cells in Patients with Recurrent High-Grade Glioma: Initial Results and Work in Progress.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11006657.html