Estimation of upper limits on human radiation absorbed doses from carbon-11-labeled compounds.
Radiation absorbed dose estimates for short-lived PET tracers are commonly based on biodistributions in rodents which (because of more rapid distribution and other species differences) may have limited relevance to humans. The initial purpose of this study was to estimate an intravenously injectable quantity of 11C which could not, on a priori grounds, exceed regulatory limits on radiation absorbed doses for individual organs. Upper limits on organ cumulative activities were estimated by assuming that 11C-labeled compounds are instantaneously distributed in the blood plasma, and then transferred solely and irreversibly to a single organ. The rate-constant (min-1) for each organ was taken to be its fractional cardiac output, since the plasma volume of 3 liters is recirculated each minute. The method was extended by using measured time courses of radioactivity in human arterial plasma available from previous PET studies with several 11C compounds in place of the assumption that the injected radioactivity was initially instantaneously distributed throughout the plasma. Calculations for 11C L-deprenyl, cogentin, cocaine, N-methylspiperone, putrescine and 2-deoxy-D-glucose, assuming transfer limited to a single organ, gave the kidneys rather than the thyroid as critical organ in each case. The upper-limit self-doses were 140, 210, 320, 360, 450 and 750 mrad/mCi, respectively, indicating that 34, 24, 15, 14 and 6.5 mCi, respectively, could be administered in a single PET study. These results suggest a strategy for human studies with 11C-labeled compounds: a preliminary study at the 3.5-mCi level would yield 11C arterial plasma data which could in turn be used to give a refined upper limit on radiation absorbed doses. For many 11C compounds, this strategy would demonstrate that sufficient radioactivity could be injected to give acceptable human PET images and would avoid the death of animals for biodistribution studies.
Gatley
S J
SJ
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
D000818:Animals; D001590:Benztropine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003042:Cocaine / Q000493:pharmacokinetics; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004285:Dogs; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010215:Papio; D011700:Putrescine / Q000493:pharmacokinetics; D011829:Radiation Dosage; D012642:Selegiline / Q000493:pharmacokinetics; D013134:Spiperone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D001590:Benztropine; D012642:Selegiline; D013134:Spiperone; C039167:3-N-methylspiperone; D003847:Deoxyglucose; D003042:Cocaine; D011700:Putrescine