Potent anesthetics, administered by inhalation, revolutionized the practice of surgery by the mid-19b centuy. The historical sequence of nitrous oxide (1776), ether (1818), and cyclopropane (1882) represent a progression of successively improved general anesthetics, judged by the criteria of faster onset of analgesia and po$t-surgical washout and a wider gap between MAC and the appearance of any deleterious side effects (apnea or hypotension). The development (1) of the fluorinated alkanes and ethers; halothane (A: CF,CHClBr) and isoflurane (B: CF,CHCl-0-CF,H) mark an important advance in anesthesia. These are non-flammable agents, good muscle relaxants with minimal cardiac depression. The metabolism and toxicity of the ensuing products are yet unresolved, suggesting the need for further investigation into the pharmacology of these agents. Positron emission tomography permits quantitative measurements to be performed non-invasively in man. The clearance response A(t) to an impulse 6 (t) in the lung is the integral kernel characterizing the kinetics to be expected from a more complex respiratory maneuver. The time course of the regional distribution of these potent anesthetics would be of considerable value in forming a rational basis for the administration of anesthesia, with the purpose of improving control over the drug delivery to the target organ, the brain, and the resulting analgesia. Halothane (A) and isoflurane (B) were exchange-labeled with 18F-fluoride by nucleophilic substitution. Radiochemical yields were investigated as a function of reaction time while varying temperature counter cation; KZ2,/K+ amino poly ether, (Et),Nf, Csi and solvent; CH,CN , DMSO, DMF and HMPA.No-carrier-added 18F-fluoride is produced via 180(p,n)18F by bombarding a 0.2 ml H,180 (15%) target with an 11 MeV proton beam (is 20 pA) from a CTI Inc negative ion cyclotron. One hundrc mCi of aqueous 18F is pneumatically transported to the reaction vessel, containing the appropriate counter-ion (typically 30 pM of K,,,/K+) for azeotropic drying in a helium stream (CH,CN; 95OC Woods metal bath). These are the standard conditions in our lab for the synthesis of I8F-2FDG (2) or "F-CH3F (3). Following drying, the supported lgF-fluoride is taken up in the appropriate solvent (CH,CN or DMSO), typically 50-100 pl of authentic anesthetic (A or B) is added as exchange substrate to the refluxing solvent, and timed samples are withdrawn to assay the extent of the incorporation into the volatile form. Figure lreviews the kinetic measurement results, coarsely scouting over temperature, solvent, and cation is the synthesis of isoflurane. Reactions leading to halothane proved to be similarly fast under these conditions. Volatile species were sampled from the head space gas, spiked with authentic anesthetics (A or B) and analyzed by gas radiochromatography (Porapak Q and Gas Chrom 220; 186O C, 5 ml/min He flow). Eluting species pass through thermal conductivity and electron capture detectors, and a NaI(Tl) pair operated in positron coincidence for low...