Antitumoral study. Nine woodchucks of both sexes, 20 to 30 months of age, with one or more hepatic tumors between 1.3 and 3.4 cm in diameter were used in this study. Two weeks prior to the start of the study, hepatic tumors for intratumoral administration of SFV-enhIL-12 or saline placebo were identified by ultrasonography (US) and confirmed by computed tomography (CT) while woodchucks were selleckchem under general anesthesia (ketamine [50 mg/kg] and xylazine [5 mg/kg] intramuscularly). On the day of treatment (week 0), median laparotomies were performed on anesthetized woodchucks, and grossly identifiable tumors were located, photographed, and measured with calipers before the injection of vector or placebo. Woodchucks then received a single dose of 3 �� 109 vp (SFV-1 and SFV-2), 6 �� 109 vp (SFV-3 and SFV-4), or 1.
2 �� 1010 vp (SFV-5 and SFV-6) of SFV-enhIL-12 or the same volume (0.6 ml) of saline (control-1, control-2, and control-3) by intratumoral injections into 10 separate sites of one tumor. Woodchucks were followed for 23 to 24 weeks and were euthanized thereafter. During necropsy, the liver was exposed, and hepatic tumors were photographed and measured. Analysis of tumor size. The sizes of tumors treated with SFV-enhIL-12 or placebo were determined by US and direct caliper measurements. For US, the Aloka ProSound model SSD-3500 high-frequency ultrasound system (Wallingford, CT) was used. Before each imaging session, the woodchuck abdomen was shaved to remove any hair. US imaging gel was applied to the abdomen to improve the contact with the transducer and to obtain a clearer image.
US is strongly reflected by the ribcage, which hinders imaging of any tissue located beneath the ribs, such as the lungs and a portion of the liver. Thus, the liver tissue accessible for US imaging may vary between woodchucks and between imaging sessions for the same woodchuck. In general, the left lateral, left medial, and right medial liver lobes were routinely accessible for imaging. During imaging, two-dimensional images were acquired in the transverse (cranial/caudal [Cr/C]), coronal (dorsal/ventral [D/V]), and sagittal (left/right [L/R]) planes. Tumor size was determined by US at week 0 prior to the administration of SFV-enhIL-12 or placebo and then at 2, 4, 6, 10, 14, 18, and 23 to 24 weeks posttreatment.
Tumor diameter measurements were obtained from the digital images captured on the hard drive of the US machine and printed on the integral image printer at the time of the study. The transducer was moved until the image showing the greatest tumor diameter was located. The image was frozen, and two points on opposite sides along the circumference of the tumor were marked. The integrated software then calculated the distance connecting the two points. Two additional points along the circumference of the tumor which describe a diameter perpendicular to the first diameter were then located Anacetrapib and marked.