Nuclear Imaging of Hormonal Receptor Status in Breast Cancer: A Tool for Guiding Endocrine Treatment and Drug Development

Abstract

Breast cancer is a commonly occurring disease in women and a major cause of morbidity and mortality. In the past decades, the development of medical endocrine therapies has led to a significant improvement in treatment outcome for this type of cancer. This therapy is targeting specific hormone receptors that are overexpressed by the tumor cells. In breast cancer, estrogen and progesterone receptors are important targets and therefore the receptor status of the tumor strongly determines treatment outcome. However, the receptor status can change during the course of the disease and consequently therapy resistance can occur. Therefore, insight in the current receptor status of the tumor is essential for optimal treatment. Nuclear imaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT), could provide the means to monitor the receptor status of tumors and the receptor occupancy by medical endocrine drugs in a non-invasive manner. Thus, these imaging techniques could offer a tool to guide therapy management in the individual patient. Nuclear imaging techniques for some of the relevant receptors for treatment of breast cancer are currently available. These imaging techniques could also aid the development of novel treatment strategies like modulation of hormone receptor expression. This review will address the role of hormone receptors in breast cancer treatment, the available nuclear imaging methods for monitoring the receptor status, the potential role of nuclear imaging in therapy management and drug development.

Evaluation of 4′-[Methyl-11C]Thiothymidine in a Rodent Tumor and Inflammation Model

“…More specific information on the in vivo status of tumors may be acquired by the use of a radiopharmaceutical that is a proliferation marker, as proliferative activity is one of the key factors of malignant disease. Various approaches toward tumor-specific visualization have been described in the literature, including the use of radiolabeled amino acids (7), nucleosides (8)(9)(10), choline (11)(12)(13), and various receptor ligands (14)(15)(16)(17). Strictly speaking, only labeled nucleosides that are incorporated into DNA are true proliferation markers, but the tissue kinetics of radiopharmaceuticals tracing amino acid transport, membrane metabolism, enzyme activity, or receptor expression can be used as a surrogate marker of cellular proliferation if the activity of such processes is increased in rapidly dividing cells.…”

PET and SPECT Imaging of Steroid Hormone Receptors

“…Until now, several PET and SPECT tracers have been developed to image the SHR. Most of these radiopharmaceuticals, however, were developed for applications in oncology, in particular for imaging of receptor expression and occupancy in steroid hormone-sensitive tumors like breast and prostate cancer (Hospers et al 2008 ;De Vries et al 2007 ). So far, only a few studies on imaging of SHR in the brain have been reported.…”

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

“…Estrogen and progesterone receptors provide a system with favourable binding characteristics for the uptake and selective retention of imaging agents [22,23]. Radiolabelled estrogens and progestins with appropriate biological properties have been shown to be taken up by target sites with high efficiency and great selectivity [30,32,35,[160][161][162]. An effective breast tumour-imaging ligand should present high specific activity, high binding selectivity, which is associated to the ligand's ability to differentiate the target receptor from other receptors and non-specific proteins, and also an adequate metabolic and pharmacokinetic profile [23,163].…”