The preparation and gamma-scintigraphic evaluation of the in vivo distribution patterns in dogs of a series of structurally related hydantoins labeled with the positron emitting, 20.4 min half-life radionuclide, carbon-11 are described. Carbon-11 labeled HCN was collected in water or aqueous Me2SO containing carrier KCN following cyclotron bombardment of 99% N2-1% H2 gas mixture with 22 MeV protons for 1 hr at 25-35 muA. Five 11C-labeled 5,5-dialkylhydantoins, three [11C]diarylhydantoins, five [11C]-5-alkyl-5-phenylhydantoins, and five [11C]spirohydantoins were prepared by heating generally under pressure, a mixture of 11C-labeled KCN, which was produced by isotopic exchange with carrier KCN, the corresponding aldehyde or ketone, and excess (NH4)2CO3 in aqueous ethanol or Me2SO solvent. The 11C-labeled hydantoins were dissolved in 1-1.5% aqueous NaOH for intravenous administration to dogs. Total synthesis time was 70-106 min and 1-59 mCi of final product was available for conducting serial in vivo imaging for up to 2 hr or more with the gamma-scintillation camera. Carbon-11 activity from all compounds showed initial blood-pool distribution with variable concentration of activity in the brain, lungs, liver, and kidney. All of the 11C-labeled diarylhydantoins, and most having one phenyl substituent, and one having a hexamethylene moiety showed initial accumulation of 11C activity in brain. Carbon-11 labeled 5,5-diphenylhydantoin (dilantin) showed the greastest qualitative accumulation of activity in the brain. Those 11C-labeled hydantoins having a carboxyl substituent showed prominent renal concentration and urinary excretion of activity. Most 11-c-labeled hydantoins showed a progressive homogenous whole body distribution of activity in all cellular tissues of the body. The relatively uniform distribution of activity in cellular tissues and slow excretion from the body support the thesis that the pharmacologic action of the hydantoins is related to physical effects on biomembranes rather than to specific chemical interactions with cell constituents.

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A method for the evaluation of regional lung ventilation using 81mKr eluted from a rubidium generator is described. The tracer distribution at equilibrium is a function of regional ventilation, not of volumes. The study can be performed on a wide range of patients, including unconscious and mechanically ventilated patients, and can be performed immediately following or concurrently with a perfusion study. Thus, precisely comparable ventilation and perfusion images can be obtained.

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