Creating Biomedical Technologies to Improve Health

ABOUT NIBIB

Dale Kiesewetter, Ph.D.

Dale Kiesewetter
Chemist

BG 10 RM B2C315 10 Center Dr Bethesda MD 20814

Telephone: 
301-451-3531
Program Area: 

Biography

Dr. Kiesewetter received a B.S. in chemistry and mathematics from Eureka College and subsequently obtained his Ph.D. from the University of Illinois at Urbana-Champaign. He was a student of Professor John Katzenellenbogen, a pioneer in the application of organic synthesis to study steroid hormone receptors. His Ph.D. thesis described the stereoselective radiochemical synthesis 16α-[18F]fluoroestradiol. This fluorine-18 radiolabeled steroidal estrogen has been explored for clinical application in human breast cancer throughout the years since its initial description.

Following his graduate work, he joined the group of Dr. William C. Eckelman at the NIH Clinical Center and continued work to develop novel fluorine-18 molecules directed toward the study of the muscarinic receptor system and applications in oncology.  One of the muscarinic compounds, [18F]FPTZTP, was evaluated at the NIH Clinical Center for applications in mental diseases. [18F]Paclitaxel, an analog of the clinical anticancer agent was prepared and is currently under evaluation in human subjects at the NCI.

Following the arrival of Dr. Shawn Chen and creation of the Laboratory of Molecular Imaging and Nanomedicine, Dr. Kiesewetter has been the section chief of the Chemistry and Radiochemistry Section.

Research Interests

The primary research interest is the development of methods to radiolabel biologically relevant molecules in which the introduction of 18F can be easily and efficiently accomplished.  Examples of these small molecules include the anticancer drug analog [18F]Paclitaxel, the HIV drug analog [18F]FPMPA, and the muscarinic agonist [18F]xanomeline.  An expansion of this interest is  the preparation of small radiolabeled organic prosthetic groups that can subsequently be used to radiolabel larger molecules, such as peptides or proteins. Prosthetic groups may contain hydroxysuccinimidyl esters for selective conjugation with lysine residues or maleimidyl moieties for selective conjugation with cysteine residues. Recently, we described the conjugation of [18F]FBEM (fluorobenzoylaminoethyl maleimide) with HER2-specific Affibody molecule, an scVEGF fragment and with a cysteine-containing analog of exendin-4.  These projects have yielded radiotracers with potential clinical applications.

In order to extend the probes available for PET, we have explored other available radionuclides.  The group previously had collaborative projects in the use of Br-76 (t1/2 16.2 h) and Zr-89 (t ½ 78.4h). The synthesis of NOTA modified peptides that allow complexation of [18F]aluminum fluoride as well as Ga-68 (t1/2 68 min) and Cu-64 (t1/2, 12.7 h) are used extensively in the laboratory.

Selected Publications