Synthesis of [18F]2B-SRF101: A Sulfonamide Derivative of the Fluorescent Dye Sulforhodamine 101

Title:Synthesis of [18F]2B-SRF101: A Sulfonamide Derivative of the Fluorescent Dye Sulforhodamine 101

Volume: 10 Issue: 3

Author(s): Ingrid Kreimerman, Williams Porcal, Silvia Olivera, Patricia Oliver, Eduardo Savio*Henry Engler

Affiliation:

• Ricaldoni 2010, Postal Code 11.600, Montevideo,Uruguay

Keywords: Fluorine-18, Positron emission tomography, radiopharmaceutical, Sulforhodamine 101, sulfonamide, astrocyte marker.

Abstract: Background: The red fluorescent dye Sulforhodamine 101 (SR101) has been used in neuroscience research as a useful tool for staining of astrocytes, since it has been reported as a marker of astroglia in the neocortex of rodents in vivo. The aim of this work is to label SR101 with positron emission radionuclides, in order to provide a radiotracer to study its biological behavior. This is the first attempt to label SR101 by [18F], using a chemical derivatization via a sulfonamidelinker and a commercially available platform.

Methods: The synthesis of SR101 N-(3-Bromopropyl) sulfonamide and SR101 N-(3- Fluoropropyl) sulfonamide (2B-SRF101) was carried out. The radiosynthesis of SR101 N-(3- [18F]Fluoropropyl) sulfonamide ([18F]2B-SRF101) was performed in a TRACERlab® FX-FN. Different labeling conditions were tested. Three pilot batches were produced and quality control was performed. Lipophilicity, plasma protein binding and radiochemical stability of [18F]2BSRF101 in final formulation and in plasma were determined.

Results: SR101 N-(3-Bromopropyl) sulfonamide was synthetized as a precursor for radiolabeling with [18F]. 2B-SRF101 was prepared for analytical purpose. [18F]2B-SRF101 was obtained with radiochemical purity of (97.0 ± 0.6%). The yield of the whole synthesis was (11.9 ± 1.7 %), nondecay corrected. [18F]2B-SRF101 was found to be stable in final formulation and in plasma. The octanol-water partition coefficient was (Log POCT = 1.88 ± 0.14). The product showed a high percentage of plasma protein binding.

Conclusions: The derivatization of SR101 via sulfonamide-linker and the first radiosynthesis of [18 F]2B-SRF101 were performed. It was obtained in accordance with quality control specifications. In vitro stability studies verified that [18F]2B-SRF101 was suitable for preclinical evaluations.

Cite this article as:

Kreimerman Ingrid, Porcal Williams, Olivera Silvia , Oliver Patricia, Savio Eduardo*, Engler Henry, Synthesis of [18F]2B-SRF101: A Sulfonamide Derivative of the Fluorescent Dye Sulforhodamine 101, Current Radiopharmaceuticals 2017; 10 (3) . https://dx.doi.org/10.2174/1874471010666170928112853