"The Synthesis and Biological Evaluation of Integrated and Conjugated Re/tc-99m-Containing ""3+1"" and Cyclopentadienyltricarbonyl (Cptm) Estrogen Complexes as Receptor-Based Imaging Agents for Breast Cancer"

Skaddan, Marc Bradley

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https://hdl.handle.net/2142/84459 Copy

Description

Title

"The Synthesis and Biological Evaluation of Integrated and Conjugated Re/tc-99m-Containing ""3+1"" and Cyclopentadienyltricarbonyl (Cptm) Estrogen Complexes as Receptor-Based Imaging Agents for Breast Cancer"

Author(s)

Skaddan, Marc Bradley

Issue Date

1999

Doctoral Committee Chair(s)

Katzenellenbogen, John A.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Engineering, Biomedical

Language

eng

Abstract

"The conjugated complexes herein involve estradiol substituted at the 7alpha position with rhenium and technetium complexes based on the ""3+1"" and cyclopentadienyltricarbonyl designs. The first set of complexes utilize a hexyl tether to bridge the metal-containing moiety to the 7alpha position of estradiol. The highest binding affinity for this series of complexes was observed with a ""3+1"" complex bearing an bis(2-mercaptoethyl)methyl amine as the tridentate ligand (66, 45%) and a CpTR complex employing an amide linkage (67b, 24%). Studies showed that the Tc analogs were too lipophilic for in vivo use, so we pursued the synthesis of CpTR amides containing ether functionalities in the 7alpha side-chain. This led to two new complexes: short-chain monoether complex 88, and long-chain polyether complex 87. Both retained good binding affinity, and both were more polar to some extent. However, tissue distribution studies of the Tc analogs showed no significant change from the original amide 67b, although uptake in many non-target organs was lower."

Graduation Semester

1999

Type of Resource

text

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http://hdl.handle.net/2142/84459

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