Re(I) tri-carbonyl based radiopharmaceuticals: Synthesis, in vitro studies, and protein complexation

• Main Author: Binkley, Sarah L
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2016
• Subjects: Biochemistry; Chemistry; Inorganic chemistry
• ISBN: 9781369463590; 1369463596

99mTc is the most used radionuclide in diagnostic nuclear medicine. Technetium small molecule imaging agents are being used to image almost every tissue in the body, from heart and bones, to the difficult imaging of brain tissue. Though there are many 99mTc complexes currently in use, the search for an ideal technetium radiopharmaceutical is ongoing. Ideal imaging agents must be robust enough to withstand complex biological conditions and ensure clearance from the body, yet selective enough to reach their target tissues for successful scanning. Recent work has shown that compounds based on the fac-99mTc(I)(CO)3 + core exhibit increased stability and resistance to decomposition. The chemistry and pharmacokinetics of these complexes can be safely explored using the non-radioactive, isoelectronic Re(I)(CO)3+ species. Medically useful isotopes of rhenium, 188Re and 186Re, add to the potential applications of this chemistry. In this dissertation we describe the synthesis and metathesis of [Re(CO) 3(TAME)]X (where X= Br-, Cl-, NO 3-, ClO4-, and PF6 -), and its toxicity in both primary and immortal cell culture lines. The toxicity of the parent molecule, [Re(CO)3(OH2) 3]Br, in HeLa-S3 cell culture is explored. The preparation and characterization of a Re(CO)3+-lysozyme adduct is discussed. Additional studies of the efficacy of [Re(CO)3(OH2)3]Br as an X-ray contrast agent and the preparation and partial characterization of an Re(CO)3+-insulin adduct is also described herein.