In vivo ³¹P nuclear magnetic resonance spectroscopy of rat 9l gliosarcoma treated with BCNU: Dose response of spectral changes

The 9L gliosarcoma, grown subcutaneously in juvenile Fischer 344 rats, was studied by in vivo ³¹P NMR spectroscopy following treatment with 1,3‐bis(2‐chloroethyl)‐ 1‐nitrosourea. Dose‐dependent increases in the proportion of high‐energy phosphates were observed for doses between 10 and 36 mg/kg (from 80% of the LD₁₀ to greater than the LD₅₀). These doses reduced clonogenic cell survival in a dose‐dependent fashion by as much as 3 log orders and resulted in up to 16 days of growth delay (to pretreatment tumor volume). Increases in high‐energy phosphates (relative to P_i) in the tumor were greater at higher doses despite the higher levels of clonogenic cell killing and the substantial host Systemic toxicity.