99mTc-glutamate peptide 3-aminoethyl estradiol

A favorable prognosis of estrogen therapy for breast cancer can often be predicted on the basis of response to the hormone because the estrogen receptor (ER) is a valuable marker to determine treatment outcome (1). The ER status of the tumors determines the likelihood of a favorable response to the treatment, and patients with ER-positive tumors have a better chance of recovery compared to those with ER-negative tumors. The presence of ER in the tissue is measured in a biopsy sample or after resection of a tumor. The random biopsy or tumor sampling may yield a false negative result because primary tumors usually have a heterogeneous ER distribution (2). In this regard a radioscintigraphic procedure could be more useful to determine the ER status of tumors because agents used for scintigraphy have a binding specificity for their targets. Tamoxifen is a selective ER modulator that blocks estrogen binding to the receptor and is often used to treat breast cancer. Using radioactive halogen ([18F] fluorine and [131I] iodine) derivatives of tamoxifen in conjunction with positron emission tomography (PET), some investigators have investigated and monitored the effects of this drug at the cellular and clinical levels for the treatment of cancer (3-6). Although the results obtained from these studies are encouraging, the expenses, availability, and water solubility of these derivatives are limiting factors for clinical use. As an alternative, Takahashi et al. decided to develop a meta-stable, technetium (99mTc)-labeled derivative of estradiol (EDL) to possibly investigate and monitor ER status in cancer patients because the isotope is inexpensive and easily available, and the derivative is water-soluble (7); this estradiol was conjugated to a poly-glutamate peptide (GAP) that could chelate the 99mTc isotope to obtain 99mTc-GAP-EDL for imaging and radiotherapeutic purposes. The investigators also explored the possibility of using 99mTc-GAP-EDL to detect endometriosis, an ER-associated condition, using a rabbit model (7-9).