Steroid Receptor Ligands for Breast Cancer Targeting: An Insight into Their Potential Role As Pet Imaging Agents

Abstract

The design and development of radiolabelled steroid derivatives has been an important area of research due to their wellknown value in breast cancer targeting. The estrogen receptor (ER) and progesterone receptor (PR) are important biomarkers in the diagnosis, prognosis and follow-up of the therapeutic response of breast tumours. Thus, several radioligands based on estrogens and progestins have been proposed for targeted functional ER imaging. The aim of this review is to survey and analyze the developments in this field, which have led to the design of a number of PET steroid-based imaging agents, a few of which seem to be promising as radiopharmaceuticals for detection of ER-positive breast tumours.

Small Molecules for Active Targeting in Cancer

“…Preclinical evaluation in a murine model showed high accumulation of 43 in ER + uterus and ovarian tissues . Clinical development and efficacies of 43 and related agents have been reviewed . Briefly, uptake of 43 is receptor mediated and it is effective in detecting local and metastatic breast cancer.…”

Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation

“…Progesterone receptor (PR) is overexpressed in 70% to 80% of breast cancers and in a similar subset of ovarian cancers, uterine cancers, and prostate cancers . There is an abundance of accumulating data clearly suggesting that loss of PR expression in breast cancer is associated with more aggressive tumors and worse prognosis .…”

Synthesis and biodistribution of 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2-oxo-ethoxy-phenyl]-1,2-di- (p-hydroxyphenyl)but-1-ene for tumor imaging

“…Diagnostic imaging can be achieved by administration of a suitably radiolabeled ligand that accumulates in the receptor-positive tumor cells where it can be detected and quantified by imaging. Such images can sometimes be used to predict whether hormone therapy might be effective or not [5][6][7][8]. Therefore, the development of such hormone receptor ligands for diagnostic imaging is a promising area of research.…”

“…Diagnostic imaging of breast by positron emission tomography (PET) is well established [15] and has been achieved using steroids labeled with fluorine-18 such as 16α- [16]. Although a number of steroids labeled with bromine, fluorine and iodine radioisotopes have been prepared and studied [17][18][19][20][21][22][23][24][25], especially in terms of their potential for selective radiotherapy, their use in imaging studies, particularly in humans, has been more limited. While most of these agents were based on steroidal estrogens, a few investigations were focused on nonsteroidal estrogens or antiestrogens including selective ER modulators (SERMs) [3].…”