In vivo distribution of [11C]-busulfan incynomolgus monkey and in the brain of a human patient

Summary The in vivo distribution of the antileukemic agent busulfan labeled with the positron-emitting radionuclide carbon 11 was investigated in cynomolgus monkeys and in a human patient using positron emission tomography. After i.v. injection of the radiotracer, its regional uptake was monitored for about 1 h in the monkey's body and in a separate experiment, in the monkey's brain. The concentration of radioactivity in the liver, which showed the highest levels of all the organs scanned, increased throughout the experiment and was 9-fold that in the brain at the end of the experiment. [¹¹C]-Busulfan rapidly crossed the blood-brain barrier. The radioactivity peaked in both the cortex and the white matter showing a ratio of 1.25, at 3 min but declined quickly to yield a ratio of approximately 1 after 30 min. In the human brain, radioactivity in the cerebellum, cortex, and white matter reached a maximum within 5 min showing a cortex:white matter ratio of 1.6. The activity in the cortex declined to yield a ratio of 1 within 30 min. Of the delivered dose, 20% penetrated into the brain.Abbreviations CSF cerebrospinal fluid - AML acute myelocytic leukemia - BMT bone marrow transplantation - PET positron emission tomography - BBB blood-brain barrierThis work was supported by grants from the Swedish Cancer Society (2805-B90-01X) and the Swedish Medical Research Council (B9012X0827603A and B9012P0843102B)