Approximately 18 h prior to exposure, food was removed from each animal’s cage to minimize the occurrence of radiation-induced emesis. On the day of irradiation, NHPs were administered an antiemetic, Zofran (Glaxo-SmithKline, 5 Moore Dr., Research Triangle Park, Durham, NC 27713 USA) or Ondansetron, (Hospira, Inc., 275 North Field Dr., Lake Forest, IL 60045 USA) (1–2 mg kg−1 IV or IM), 45–90 min prior to exposure. Anesthetized NHPs were placed in a Plexiglas supine restraint device, and then transported from the NHP housing area to the linear accelerator (LINAC) facility at the University of Maryland, Department of Radiation Oncology.
The NHPs were administered xylazine to ensure proper radiation field placement would be maintained and then exposed to PBI/BM5 with 6MV LINAC-derived photons. PBI was delivered at an approximate dose rate of 0.80 Gy min−1. The MLTD doses delivered included 9.0 Gy, 10.0 Gy, 11.0 Gy, 11.5 Gy, 12.0 Gy, and 12.5 Gy. Animals were positioned such that their tibiae were outside of the beam field. Animals were observed via in-room cameras throughout the exposure procedure. Following PBI, NHPs were anesthetized, transported back to the NHP housing area, administered Lactated Ringer’s Solution (LRS) (10–15 mL kg−1 IV) and a second dose of Zofran or Ondansetron (1–2 mg kg−1 IM or IV), and returned to their home cage.
Prior to beginning the study, the LINAC was calibrated in the geometry used for NHP irradiation. Depth dose measurements were made at the center of a cylindrical phantom that approximates the mean diameter of the experimental rhesus macaque. Three phantoms of increasing size were available. The phantom is made of 0.32-cm Lucite and filled with water. Dose measurements were performed with ion chambers. Absorbed dose to water per unit machine monitor unit (MU) was obtained. The calibration was then transferred to a constancy system for daily quality assurance purposes.
During NHP irradiations, in vivo dosimetry was performed using a silicon diode system. One diode was placed on the chest to measure the delivered dose, and another was secured on the tibiae to confirm that the tissue outside of the beam field was spared irradiation. Quality assurance and control procedures that were performed prior to each set of NHP irradiations included LINAC energy output checks and diode calibrations.