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

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 chem-ical derivatization via a sulfonamide-linker 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 sta-bility of [18F]2B-SRF101 in final formulation and in plasma were determined.Results: SR101 N-(3-Bromopropyl) sulfonamide was synthetized as a precursor for radio-labeling 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%), non-decay corrected. [18F]2B-SRF101 was found to be stable in final for-mulation 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 radiosyn-thesis of [18F]2B-SRF101 were performed. It was obtained in accordance with quality con-trol specifications. In vitro stability studies verified that [18F]2B-SRF101 was suitable for preclinical evaluations.

Biological Assessment of a 18F-Labeled Sulforhodamine 101 in a Mouse Model of Alzheimer’s Disease as a Potential Astrocytosis Marker

“…Thus, it has been proposed that astrocytes are labeled before oligodendrocytes (Wasseff and Scerer, 2011; Hill and Grutzendler, 2014; Anderova et al, 2016; Hagos and Hülsmann, 2016). We have confirmed 2B-SRF101’s ability to detect astrocytes in cell cultures with a higher affinity than that of SR101 (Kreimerman et al, 2017). In the present work we performed a biological characterisation of the new tracer including biodistribution and micro-PET/computed tomography (CT) images.…”

“…[ 18 F]2B-SRF101 was synthesized according to the method previously reported by our group (Kreimerman et al, 2017). A solution of the precursor SR101 N -(3-Bromopropyl) sulfonamide (1 mg in 1 mL of dimethyl sulfoxide, DMSO) was added to a preactivated and dried [ 18 F]-fluoride solution.…”

“…To develop a new agent for detecting astrocytosis and overcoming the difficulties previously described, we recently reported the synthesis of a sulfonamide derivative of Sulforhodamine 101 (SR101) labeled with 18 F, namely SR101 N -(3-[ 18 F]Fluoropropyl) sulfonamide ([ 18 F]2B-SRF101). In vitro studies of this compound indicated physicochemical and biological properties appropriate for neuroimaging (Kreimerman et al, 2017). The red fluorescent dye, SR101, has been used as a specific marker of astroglia in the neocortex of rodents using in vivo models (Nimmerjahn et al, 2004; Nimmerjahn and Helmchen, 2012).…”

Dosimetry and Toxicity Studies of the Novel Sulfonamide Derivative of Sulforhodamine 101([18F]SRF101) at a Preclinical Level

“…[ 18 F]SRF101 was synthesised according to the method previously reported by our group [1]. A solution of the precursor SR101 N-(3-Bromopropyl) sulfonamide (1 mg in 1 mL of DMSO) was added to a pre-activated and dried [ 18 F]fluoride solution.…”

“…The SR101 N- (3-[ 18 F]Fluoropropyl) sulfonamide ([ 18 F]SRF101) is a Sulforhodamine 101 (SR101) derivative that was previously synthesised by our group [1]. The fluorescent dye SR101 has been reported as a specific marker of astroglia in the neocortex of rodents in vivo [2,3].…”