International Journal of Applied Radiation and I~otopes, Vol, 29. pp. 225 227 11(/2t~-7(18X 78 0501-0225~-(~2 iX) 0 © Pergamon Press. Lid,, 1978. Printed in Great Britain The Synthesis of 13N-Labelled Nitrous Oxide R. J. NICKLES, S. J. GATLEY, R. D. HICHWA, D. J. SIMPKIN and J. L. MARTIN Department of Radiology, University of Wisconsin. Madison. W! 53706. U.S.A. (Received 18 August 1977; in revised form 12 December 1977) A pair of methods is described for the synthesis of 13N20 by pyrolysis of NH4NO 3 in sulfuric acid. Both methods start with t3NO 3 production via the proton irradiation of water. The methods differ in the use of precursor I3NO 3 or 13NH,~ formed by nitrate reduction with DeVardas alloy. A 30~o contamination with 13N2 is common to both methods, but this falls to less than 2j'~/o when a ten-fold excess of NH2 over 13NO 3 is used. Millicurie activities of 13N20 in 4mM of carrier result from 18min of processing with a decay-corrected yield of 80~o. This yield encourages the use of 13N20 as a positron-emitting tracer for the measurement of cerebral blood flow. 1. INTRODUCTION INERT, diffusable tracers play a key role in the measurement of physiological flow processes. Nitrous oxide, for example, has been used to assess total cere- bral blood flow by the Kety-Schmidt method/1~ These studies have been largely supplanted by radionuclide tests employing such gamma-ray emit- ters as zaaxe which offers regional information with- out the need for blood sampling/2~ Furthermore, the lower solubility of xenon relative to nitrous oxide shortens the blood-tissue equilibration time, facilitat- ing the measurement of flow-dependent washout. On the other hand, N20 labelled with 13N or 150 would permit tomographic localization t3J with the new gen- eration of positron-coincidence imaging devices/4'5'6~ In this event, the increased solubility of N20 results in two significant advantages. First, the greater signal due to the increased concentration in the field of view results in a better utilization of the tracer and the limited singles count rate capability of the instrument. Secondly, the slower dynamics of cerebral N20 wash- out are better matched to the current scanning time requirements. For these reasons, a program was in- itiated to synthesize a number of positron-emitting anesthetic gases, most notably 13N20. 2. MATERIALS AND METHODS The strategy used in these methods follows the preparation of N20 by the pyrolysis of NH4NO3 in sulfuric acid/7~ Nitrogen-13 is produced via the 160(p,ct)13N reaction by proton irradiation of water at 10 MeV on the U.W. Tandem accelerator. Target conditions on the beam axis are monitored by fiber optics telemetry. The 1.5-p.A proton beam results in 6mCi of labelled NO3 ta'9~ at saturation, measured by a flow-through positron detector ~1°~ in the recircu- lating target flow loop. After bombardment, l mM of NH4NO3 was added to the 20ml of irradiated H20, and one of two routes was then followed to N20. Method I Carrier NO~- and 13NO 3 were reduced with DeVarda's alloy Ill~ to NH 3 which was distilled from basic solution and collected by bubbling through 25 ml of cold H2SO4 which contained an additional 3 mM NH4NO3. The apparatus was swept by a N z gas stream. The H2SO 4 was heated to 260°C and N20 produced by the reaction NHaNO 3 --* N20 + 2H20 (1) was quantitatively evolved and collected over water. More vigorous dehydration with fuming H2SO4 (20~o excess SO3) proved unnecessary. The final tempera- ture of 260°C was that at which the rate of evolution of gas began to balance the rate of decay of the ~3N20 already collected. Method 2 The irradiated water was combined with carrier NHgNO 3 and concentrated to l ml by rotary evapor- ation. Care was required to avoid loss of ' 3NO 3 dur- ing de-gassing. Twenty-five ml of H2SO4 containing 3 mmol of additional NH4NO3 was added and N20 evolved at 260 as in method I. Analysis Gas radiochromatography (RGLC) was performed (Porapak Q and molecular sieve 5A; 65°C; 5 ml/min He carrier) to assay the radiochemical purity of each batch of 13N20. Decay correction was applied to the activity trace of the RGLC to account for the l0 rain half-life of 13N. Tests with authentic N20 show less than 2~/o decomposition to N 2 in passage through the RGLC at the temperature used in this study. It warrants mention that three previous attempts at 13N20 production proved unsuccessful. First, direct deuteron irradiation of COz with 5°0 N20 carrier showed less than 2°0 of the 13N-activity associated 225