Volumetric MRI scans and FDG/PET scans of the brain will be obtained to assess the pretreatment size 
and metabolic activity of the tumor. The major anatomic goals will be to define volume of enhancing 
tissue as measured on T1 -weighted" volumetric gradient-echo image sets obtained before and after 
administration of gadopentate dimeglumine contrast material [43]. The volume of edema detected on Fast 
Spin-Echo “T2-weighted“ images will be determined. This will include portions of the neoplasm, white 
matter infiltrated by neoplastic cells and vasogenic edema located beyond the confines of the tumor. The 
presence and severity of mass effect will be evaluated using linear measurements on the T1- and T2 
weighted images. The volumetric MRI scans will be superior to standard MRI scans because they will 
permit more accurate estimation of tumor volume, and shape. This technique will be helpful in 
determining the areas of the tumor to be injected and for calculating the virus dose per unit volume in 
these irregularly shaped and inhomogeneous tumors. 
The positron emission tomography technique with F-18 fluoro-deoxy glucose (FDG) is able to identify 
high grade tumors (high glucose metabolic rate) and differentiate necrosis (low glucose metabolic rate) 
from recurrent tumor more reliably than MRI scan [44, 45]. Prior studies have demonstrated that the 
glucose metabolic rate falls prior to a clinical response to cancer treatment [46, 47]. FDG-PET thus 
will give us an independent method for following tumor response. 
III.B.3 Clinical Trial 
The patients will be admitted to the neurosurgery service and evaluated to establish that their clinical 
status has not changed from their initial evaluation. The patient will be prepared for surgery with 
dexamethasone and an anticonvulsant, and taken to the operating room for stereotactic surgery . An MRI 
compatible Cosman-Roberts-Wells (CRW) stereotactic frame (Radionics, Inc., Burlington, MA) will be 
placed on the patients head under antiseptic technique using local anesthesia. The patient will then be 
taken to the MRI scanner where the tumor will be localized by MRI scan with gadopentate dimeglumine 
contrast. 
The tumor measurements from the MRI scan will be analyzed using Stereoplan™ software program 
(Radionics, Inc.). A three dimensional representation of the tumor will be constructed identifying the 
points of injection and depths of injection to be utilized to provide complete infiltration of tumor. The 
patient will be returned to the operating room, placed under general anesthesia, and the CRW arc will be 
attached. The tumor will be stereotactically infiltrated with H5.010RSV77C. The virus will be injected 
slowly so as to prevent the virus suspension from extravasating along the 22 gauge needle injection 
tract. We anticipate that we will be injecting tumors varying in size from 20 to 50 cm 3 with an 
average of 35 cm 3 in volume. In the two phase I studies we initially plan to treat a total of 18 patients. 
In each study (resectable and unresectable tumors) there will be three patients at each dose of virus 
(10 9 , 1010, anc j -jo 11 pfu). The total virus volume will be 200 pi. Postoperatively, the patient will 
be treated with prophylactic antibiotics (either cefazolin or vancomycin). The patient will remain in a 
private room on the surgical intensive care unit under continuous observation for signs of increased 
intracranial pressure. Serum electrolytes, urine specific gravity and neurologic status will be 
monitored. Examinations will be performed daily, or more frequently, by a neurosurgeon and a 
neurologist who are investigators. On the second postoperative day, intravenous ganciclovir will be 
started at a dose of 5mg/kg IV over one hour, every 12 hours, and continued for 14 days, or until the 
second surgery (in the case of patients with resectable lesions). When clinically stable, the patient will 
be transferred to the GCRC. This is expected to be 1 to 2 days postoperatively. Standard MRI scans will 
be repeated within 48 hours and volumetric MRI scans at 7 days after surgery, or earlier if a 
significant change in size of tumor is suspected by the standard MRI. Seven days after stereotactic 
surgery, the patients in the phase IA study will undergo open craniotomy. This will provide debulking of 
a recurrent tumor which is the standard procedure for a patient with good performance status and tumor 
in a resectable location, and tissue to be analyzed for effects of gene therapy. At the time of the second 
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Recombinant DNA Research, Volume 20 
