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NCI172112 is a classical bifunctional alkylating agent synthesized in an effort to develop antitumor agents effective against CNS tumors.

NCI172112 (Spirohydantoin mustard, SHM) might serve as a carrier to cross the blood brain barrier. The cumulative excretion of radioactivity in the urine and faeces of rats after administration of [2-chloroethyl-U-C]NCI172112 or [hydantoin-4-C]NCI172112 ( 3.13 mg/kg. i.v.) is measured. Four hours after dosing, a significantly (P<0.005) greater amount of radioactivity has been excreted in the urine of rats treated with [hydantoin-C]NCI172112 than with [ethyl-C]NCI172112. However, by 24 h, approx.50% of dose is recovered in the urine with both labelled materials. Clearance of radioactivity in the faeces is slow, but, as for the renal excretion, is significantly greater for the hydantoin-C moiety. No radioactivity is found in the expired air of a rat receiving a single dosing of [hydantoin-C]NCI172112 and less than 1% is measured after administration of [ethyl-C]NCI172112. Renal clearance of radioactivity is similar 4 h after administration of [C]NCI172112 to rats with biliary cannulas, with 14.1±2.9 and 17.5±2.1% of the ethyl-C and 34.5±2.5 and 33.1±6.3%, of the hydantoin-C dose appearing in the urine after dosing with 3.13 and 6.25 mg/kg, respectively. A difference in the 4 h urinary excretion of the two labels also is observed in dogs given [C]NCI172112 (1 mg/kg, i.v.). The percentages of hydantoin-C and ethyl-C eliminated are 29.4±2.7% and 17.2±3.5%, respectively (P<0.05).

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