Evaluation of novel radioiodinated C7-substituted Δ^6,7-estradiol derivatives for molecular recognition of er-positive breast tumours

The estrogen receptor is a striking target for molecular imaging and therapy of certain malignancies. In the case of cancer, the ability of imaging the expression of the ER would offer a noninvasive means of classifying tumours guiding the optimal choice of therapy. The importance of estradiol based radioligands as potential imaging agents for estrogen re-ceptor rich tumours and the growing interest in Auger electron emitters for potential radiotherapy of estrogen receptor-positive breast cancers lead to the synthesis and evaluation of a series of radioiodinated derivatives of estradiol. Seeking for new probes for targeting the estrogen receptor two novel radioiodinated Δ^6,7-estradiol derivatives containing different C7-alkyl chains were prepared and labelled with ¹²⁵I. To evaluate the potential use of their ¹²³I-analogues for im-aging breast tumours the biological behaviour of the new radioligands was studied in immature female rats to determine their uptake in and selectivity for tissues containing estrogen receptors. The different alkyl chains induced major modifi-cations in the uptake efficiency, selectivity and in the metabolization degree of the compounds. It is not very clear, how-ever, whether the alterations in uptake efficiency and selectivity are the result of differences in lipophilicity or altered pat-terns of metabolism. Even so, these radioligands exhibit different biological patterns that may be helpful in optimizing the imaging of ER positive tumours.