Synthesis and Testing of Gadolinium Derivatives of Hormones

Grant Winner

Dean

Abstract

The detection of cancerous mammary tumors is usually achieved in the earliest stages by mammography, and in later stages by palpation. Early detection is advantageous for lumpectomy excision or treatment. However, in the case of either very dense breast tissue, the presence of fibrocystic disease or implanted prosthesis, these lesions can be obscured until their size is dangerously large. Advanced development of such lesions makes more likely the possibility that they have either spread to lymph nodes, or metastasized to distant locations.

Magnetic resonance imaging can under the right conditions give exquisitely detailed pictures of soft tissue lesions. In the case of mammary tumors, the complicating tissue components and the lower sensitivity of non-enhanced MRI than mammography to tumor size makes MRI less than optimal in its performance. For these reasons, the use of paramagnetic compounds has been explored by several workers in order to enhance breast tumor appearance in MR images. Currently, such contrast agents are non-specific, going throughout the bloodstream with no particular localization. This makes the utility of such agents with breast lesions very time dependent, because the agent will eventually be equally distributed throughout the vascular pool.

For the above reasons, I propose to synthesize gadolinium-DTPA derivatives of the hormones prolactin, placental lactogen, and oxytocin. It is well established that these hormones have membrane receptors in mammary tissues. If time permits, a DTPA derivative of estradiol will also be synthesized, although estrogens bind only transiently to cell surface proteins. The possible interaction of the gadolinium-DTPA-hormones with cultured mammary tumor cells will be measured by determining the proton T1 and T2 relaxation times of the water in samples of packed tumor cells both with and without the gadolinium-DTPA complexed to the various hormones, and bound to the cells.