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[ 3 H]RU38486 (RU486) was synthesized from its penultimate precursor, desmethyl RU486, by substitution of the secondary amine with tritiated methyl iodide ; specific activity 85 Ci/mmol. Ligand binding studies confirm that RU486 binds with high affinity to human progesterone receptor type A (PR-A) and progesterone receptor type B (PR-B).

LGD1069, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl] benzoic acid, is the first retinoid X receptor (RXR) selective retinoid to enter clinical trials for treatment of dermatological diseases and cancer. In order to examine biological properties such as receptor binding, metabolism and bioavailability, [ 13 C]-[ 14 C]-, and [ 3 H]-labeled LCD1069 is required. Herein, we describe synthetic methods for preparing isotopically labeled homologs of LGD 1069 as well as comparative competition binding data for [6,7- 3 H]-LCD1069 and [ 3 H]-9-cis retinoic acid with RXR active retinoids. The final radiolabeled products, [6,7- 3 H]-LGD 1069 and 3-[ 14 C]-LGD1069 have specific activities of 56 Ci/mmol and 49 mCi/mmol, respectively. Radiochemical purities are 99.5% for [6,7- 3 H]-LGD1069 and 99.0% for 3-[ 14 C]-LGD1069. The chemical purity is 99.0% for 3-[ 13 CD 3 ]-LGD1069. Competition binding studies with known retinoids show similar Kd values when either [6,7- 3 H]-LCD1069 or [ 3 H]-9-cis retinoic acid is used as the radioligand

Radioiodination of methyl-7-[(2R, 2S, 3S, 5R)-6,6-dimethyl-3-(4-trimethylstannylbenzenesulfonylamino) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoate with [125I] Na using a modification of the chloramine-T method in organic solvent is simple with high yields and site specific. The product, following hydrolysis of the ester, 7-[(2R, 2S, 3S, 5R)-6,6-dimethyl-3-(4-[125I]-iodobenzenesulfonylamino) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid ([125I]-ISAP), was purified by HPLC. The high specific activity and specific binding will make the ligand a useful tool for the characterization of thromboxane A2/prostaglandin H2 receptors.

The synthesis of [125I]-(1S,2S,3S,5R)-2-(6′-carboxyhex-(2′Z)enyl)-3-(2-hydroxy-3- (4-hydroxy-3-iodophenyl)-1-propylamino)-6,6-dimethylbicyclo[3. 1. 1] heptane(I-PTA-OH), a high affinity thromboxane A2/prostaglandin H2, (TXA2/PGH2) receptor antagonist has been previously described. This paper describes the synthesis of an analog of this compound, [127I]- and [125F]-(1S,2S,3S,5R)-2-(6′-carboxyhex-(2′Z)enyl)-3-(2-hydroxy-3- (4-iodo-3-azidophenoxy)-1-propylamino)-6,6-dimethyl- bicyclo[3.1.1]heptane(I-PTA-azido), which has the potential to be used as a photo- affinity probe of the TXA2/PGH2 receptor. This compound, which is the highest affinity photoaffinity probe yet described for the human platelet TXA2/PGH2 receptor may be a useful tool to characterize this receptor.