The rate of response of breast cancer to anti-estrogenic treatment increases with the content of estrogenic receptors in the tumor. Currently, levels of hormone receptors are determined in biopsy samples and used as a guide to therapy. There is great interest in developing gamma-emitting radiopharmaceuticals which are analogs of major naturally occurring estrogens. Such agents would bind to receptor sites in-vivo and permit non-invasive, more accurate screening of these tumors than is currently available. However, most analogs reported to date have failed as estrogen receptor site agents due either to the nonspecificity or low specific activity of the materials synthesized. We propose to develop rapid syntheses of high specific activity (no-carrier-added) carbon-11 labeled 17 Beta-estradiol and related hormones. Since carbon-11 is chemically identical to naturally occurring carbon, the agents will be physiologically identical to naturally occurring hormones. Thus we will circumvent many of the specificity problems encountered in previous studies. We will also synthesize a nonsteroidal hormone, hexestrol, which has been demonstrated to be receptor site active. We will utilize organoborane technology to incorporate carbon-11 on a no-carrier-added scale in the final synthetic steps; thereby ensuring high specific activity of the hormones. The syntheses of carbon-11 labeled hormones will permit the use of positron emission tomography (PET) which provides three-dimensional imaging. The agents will be tested in a variety of animal species and the results of these extensive biological studies will be sued to formulate an IND for the successful agent. The new methods will be suitable for synthesizing carbon-13 labeled hormones for use in nuclear magnetic resonance imaging studies (a new and promising modality in medical diagnosis).
| Takagi, S; Ehara, K; Finn, R D (1987) Water extraction fraction and permeability-surface product after intravenous injection in rats. Stroke 18:177-83 |
| Kothari, P J; Finn, R D; Kabalka, G W et al. (1986) Carbon-11 labeled dialkylketones: synthesis of 9-[11C]heptadecan-9-one. Int J Rad Appl Instrum A 37:471-3 |
| Kothari, P J; Finn, R D; Kabalka, G W et al. (1986) Synthesis of nitrogen-13 labeled alkylamines via amination of organoboranes. Int J Rad Appl Instrum A 37:469-70 |
| Kothari, P J; Finn, R D; Vora, M M et al. (1985) 1-[11C]butanol: synthesis and development as a radiopharmaceutical for blood flow measurements. Int J Appl Radiat Isot 36:412-3 |
