11/20/2025
By Suzanne Young

The University of Massachusetts Lowell, Department of Chemistry, invites you to attend a Master’s Thesis defense by Madelyn Hallisey on “Novel PET Radiochemistry: Adapting Analytical and Semi-Preparative High Performance Liquid Chromatography Methods to Enhance the Synthesis of the Carbon-11 Radiotracer FLB457.”

Candidate Name: Madelyn Hallisey
Degree: Master’s
Defense Date: Thursday, December 4, 2025
Time: 8:30 to 10:30 a.m.
Location: OLN518, Olney Hall, North Campus
Thesis/Dissertation Title: Novel PET Radiochemistry: Adapting Analytical and Semi-Preparative High Performance Liquid Chromatography Methods to Enhance the Synthesis of the Carbon-11 Radiotracer FLB457

Committee:

  • Advisor: Olof Ramstrom, Ph.D., Chemistry, University of Massachusetts Lowell
  • Joseph Downey, Ph.D., Instructor in Radiology, Athinoula A. Martinos Center for Biomedical Imaging and Harvard Medical School
  • Suzanne Young, Ph.D., Chemistry, University of Massachusetts Lowell
  • Erin Bertelsen, Ph.D., Physics and Applied Physics, University of Massachusetts Lowell

Brief Abstract:
Positron emission tomography (PET) is an imaging technique that provides highly detailed images of organs and tissues. To obtain these images, a small amount of a radioactive tracer is administered to rodents, non-human primates, or humans. A radioactive tracer, or radiotracer, is a drug compound that has undergone a chemical reaction with a radioactive isotope. [11C] FLB457 is a carbon-11 labeled radiotracer that is used to image dopamine D2 and D3 receptors found in the striatum of the brain. Adaptation of [11C] FLB457 synthesis was last presented in 1995. Since then, technological advancements allow for synthesis improvement without compromising imaging results. In the past, [11C] FLB457 has been synthesized using [11C] methyl iodide ([11C] CH3I) with solvents including dimethyl sulfoxide (DMSO) and sodium hydroxide (NaOH). Challenges faced from using this method with current technological advancements showed a decrease in the amount of radioactivity available for administration. The goal of this project was to develop an improved method of synthesizing [11C] FLB457 by updating the chemistry, purification, and quality control analysis methods with a focus on good manufacturing practice (GMP) compliance for investigational new drug (IND) submission.

To achieve the goals mentioned, the first step was to develop high performance liquid chromatography (HPLC) methods for purification and quality control analysis. Development began following pre-established methods but yielded inadequate results involving peak tailing and asymmetrical peak shapes. To combat these challenges, mobile phase pH was adjusted and columns with more robust capabilities were used. A semi-preparative method was developed using a basic mobile phase to allow for fast and easy purification of the product. An analytical method used for quality control analysis was developed that showed repeatable results with a short method run time that allowed for confirmation of [11C] FLB457 chemical identity and radiochemical purity.

Once analytical and semi-preparative HPLC methods had been developed, experimentation began on adapting the chemical synthesis of [11C] FLB457. Conditions previously established in the 1990s were followed similarly to determine a baseline of potential yield capability. Using manual and automated chemistry, and reactor vial and “in-loop” synthesis methods, various conditions were able to be tested. Syntheses using [11C] CH3I, dimethylformamide (DMF), and tetrabutylammonium hydroxide (TBAOH) and [11C] CH3I, DMSO, and TBAOH yielded less than 10 millicuries (mCi) of final administrable activity, not a sufficient yield. Due to the insufficiencies of those conditions, additional syntheses were explored using [11C] methyl trifluoromethanesulfonate ([11C] CH3OTf), methyl ethyl ketone (MEK), and TBAOH. Through automated and “in-loop” synthesis and purification, it was determined that [11C] MeOTf, MEK, and TBAOH gave average yields of 62.4 mCi with an average radiochemical purity of 91%, sufficient administrable activity levels.