Progesterone receptor targeting with radiolabelled steroids: An approach in predicting breast cancer response to therapy

Steroid receptors have demonstrated to be potentially useful biological targets for the diagnosis and therapy follow-up of hormonally responsive cancers. The over-expression of these proteins in human cancer cells as well as their binding characteristics provides a favourable mechanism for the localization of malignant tumours. The need for newer and more selective probes to non-invasively assess steroid receptor expression in hormone-responsive tumours has encouraged the synthesis and the biological evaluation of several steroidal derivatives labelled with positron and gamma emitters. The physiological effects of the steroid hormone progesterone are mediated by the progesterone receptor (PR). Since PR expression is stimulated by the oestrogen receptor (ER), PR status has been considered as a biomarker of ER activity and its value for predicting and monitoring therapeutic efficacy of hormonal therapy has been studied. Imaging of PR-expressing breast cancer patients under hormonal therapy may be advantageous, since the response to therapy can be more accurately predicted after quantification of both ER and PR status. Thus, ligands for PR targeting, although much less explored than ER ligands, have gained some importance lately as potential PET and SPECT tumour imaging agents. In this review, we present a brief survey of explored approaches for progesterone targeting using radiolabelled progestins as potential clinical probes to predict responsiveness to breast cancer therapy. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".