A comparative study of the tissue distribution of five
tritium-labeled
androgens was done in rats to determine the efficiency and selectivity of their uptake by target tissue.
Testosterone (T),
5 alpha-dihydrotestosterone (DHT),
19-nortestosterone (nor-T),
mibolerone (Mib) and
methyltrienolone (
R1881) all showed selective uptake by the ventral prostate in one-day castrated rats (250 g) that was 61-90% displaceable by co-injection of an excess of unlabeled
steroid. The greatest uptake was with
R1881 (0.69% injected dose per gram prostate tissue (%ID/g) at 1 h), and Mib (0.56% ID/g); the other three showed lower uptake (approx. 0.4% ID/g). The target tissue activity remained high for all compounds up to 4 h after injection, and at 2-4 h the prostate to blood ratio for Mib and
R1881 exceeded 10 and 20, respectively. The uptake efficiency and selectivity of these five
androgens appear to be related to their affinity for the
androgen receptor and their resistance to metabolism. Mib and
R1881 have substantial affinity for other
steroid receptors, which might account for some of their prostate uptake. However, co-administration of
triamcinolone acetonide, which has high affinity for
progesterone and
corticosteroid receptors but not for the
androgen receptor, failed to block their uptake significantly, whereas co-administration of DHT, the most selective
ligand for the
androgen receptor, blocked their uptake as completely as the unlabeled tracer itself. The prostate uptake of Mib and
R1881 in intact animals was significantly lower than in castrated animals, but treatment of the intact animals with
diethylstilbestrol restored their uptake nearly to the level seen in castrated animals. These uptake patterns are consistent with earlier studies of in vivo
androgen uptake and with known changes in
androgen receptor content and occupancy as a result of
castration or
diethylstilbestrol treatment. They further suggest that high affinity
androgens labeled with suitable
radionuclides--particularly derivatives of
mibolerone (Mib) or
methyltrienolone (R1881)--may be effective receptor-based imaging agents for
androgen target tissues and
tumors, even when patients are already receiving hormonal
therapy.