Michael Welch

Methodology for the synthesis and specific activity determination of 16α-[77Br]-Bromoestradiol-17 β and 16α-[77Br]-11 β-methoxyestradiol-17 β, Two estrogen receptor-binding radiopharmaceuticals

Abstract 16α-[ 77 Br]-Bromoestradiol-17β ( 3a ) has been synthesized from estrone enol diacetate ( 1 ) by bromination with Na 77 Br and hydrogen peroxide-acetic acid, followed by reduction with lithium aluminum hydride to give a mixture of 16α-[ 77 Br]-bromoestradiol-17β ( 3a ) and 16α-[ 77 Br]-bromoestradiol-17α ( 3a ) from which the desired epimer ( 3a ) can be obtained in 50% overall radiochemical yield (from Na 77 Br) by HPLC. Analogous procedures can be used in the preparation of 16α-[ 77 Br]-bromo-11β-methoxyestradiol-17β. ( 4a ) The effective specific activities of these radiopharmaceuticals, determined by binding to the uterine estrogen receptor, are 900–1500 Ci/mmol. Both have high affinity and good binding selectivity for the estrogen receptor and are useful as imaging agents for mammary tumors.

Synthesis and biological evaluation of tc-99m-cyclopentadienyltricarbonyltechnetium-labeled octreotide

Octreotide was labeled at its N-terminus with Tc-99m-cyclopentadienyltricarbonyltechnetium, and the biodistribution of the labeled conjugate was studied in adult female Sprague-Dawley rats. The synthesis began with the preparation of Tc-99m-(methoxycarbonylcyclopentadienyl) tricarbonyltechnetium from Tc-99m-pertechnetate using a novel double ligand transfer reaction; it was completed in a total of five steps, with an 8% overall radiochemical yield (15% decay-corrected). The 99mTc-cyclopentadienyltricarbonyltechnetium-labeled octreotide conjugate (99mTc-CpTT-octreotide) showed receptor-mediated uptake in the pancreas and adrenals, which was blocked (80% and 93%, respectively) by excess unlabeled octreotide. These studies illustrate a new method for labeling a peptide with Tc-99m through an organometallic linkage that is stable, nonpolar, and low molecular weight; it complements labeling approaches that utilize inorganic metal complexes.

Steroid Hormone Receptors as Targets for Diagnostic Imaging

A century ago the connection between body function and cancer was first reported. In 1896, Beatson released his study of several premenopausal women who had remarkable regression of advanced breast cancers following ovariectomy, and voiced the proposal that there must be some substance in these organs contributing to the growth of the cancers. [1] The search for the factors affecting tumor death and growth had begun. Subsequent scientific advances in the areas of chemical synthesis, biology and physiology, and assay techniques brought substantial progress in the fight to understand and conquer cancer.

111In-Labeled Platelets for the Detection of Vascular Disorders in Animal Models

Radiolabeled blood components were developed to better identify various parameters including: total blood volume (Wennesland et al., 1959; Radia et al., 1981), plasma volume (Hurley, 1974), cell kinetics (Heaton et al., 1979; Heyns et al., 1980; Pastakia, 1978) and the detection of abscess or thrombosis (Goodwin et al., 1978; Coleman et al., 1980; Thakur et al., 1977; Beswick et al., 1979; Krohn and Welch, 1977).