RT Journal Article SR Electronic T1 A Unique 18F-labeled G-protein-coupled receptor 44 (GPR44) radiotracer: design, radio-synthesis and evaluation in the rodents JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 622 OP 622 VO 61 IS supplement 1 A1 Jiangling Peng A1 Wei Tang A1 Lynn Miao A1 Eryun Zhang A1 Nelson Gonzalez A1 Fouad Kandeel A1 Junfeng Li YR 2020 UL http://jnm.snmjournals.org/content/61/supplement_1/622.abstract AB 622Objectives: The G-protein-coupled receptor 44 (GPR44) plays a key role in the inflammatory diseases, and emerged as a therapeutic target in asthma and other allergic disorders. In human pancreas, GPR44 is expressed in the islets of Langerhans and not in the exocrine pancreas. GPR44 seems a reliable biomarker for assessment of islets mass, which is significant in diabetes and related diseases. However, F-18 tracer targeting GPR44 has not been reported. Of relevance, most of the reported ligand for GPR44 displays a free carboxylic acid group. Even the 18F labeling method was well developed, labeling compound including free carboxyl group in on step is still challenging. Given the short half-live of 18F, labeling compound including a free carboxyl group in one step is highly desirable. The purpose of this study was to develop an 18F GPR44 tracer, and to evaluate the tracer ex vivo in rodents. Methods: TM30089 is a selective GPR44 antagonist with excellent potency (GPR44 Ki = 0.6 nM). Radionuclide incorporation using 18F-fluoride was accomplished through nucleophilic substitution of a novel precursor derived from TM30089. The labeling experiments were preformed using the GE TRACERlabâ„¢ FN radio-synthesis module. Precursor was prepared from commercially available starting material and [18F] labeling optimized through modification in temperatures, reaction solvents and reaction times. The final product was purified by reverse phase semi-preparative HPLC. The expression of GPR44 in human islets was validated by immunofluorescence staining and Western blot. Bio-distribution studies were conducted in adult male NOD/SCID mice to determine tracer distribution. Animals were euthanized at 30, 60 and 90 minutes post-injection of [18F] Ab-1. Organs of interest were collected, weighed, and counted on an automated gamma counter. Uptake of radioactivity was calculated as percentage injected dose per gram (%I.D./g). Results: Quaternary ammonium salt precursor 8 was identified and obtained in 7 steps from commercially available starting materials. Precursor 8 was converted to [18F] Ab-1 in 15 minutes through a one-step labeling reaction. The product [18F] Ab-1 was purified by HPLC in 15.5 minutes with RCY's of ~30% and high radiochemical purity (> 98%). Immunofluorescence staining and Western blot analysis confirmed that GPR44 is expressed in isolated human islets. Initial bio-distribution studies and blocking experiment showed that low tracer uptake in murine pancreases, consistent with low expression of GPR44 in mice pancreas from other reports. Conclusions: The expression of GPR44 in human pancreases islets was confirmed. A novel tracer GPR44-targeting radiolabeled tracer, [18F] Ab-1, was produced with a synthetic protocol that gave good yield and radiochemical purity. Initial bio-distribution studies showed minimal tracer uptake in murine pancreases. Studies are ongoing to evaluate the potential of the tracer to track human islets transplanted into rodents. Further studies of [18F] Ab-1 will assess its application to beta cell mass imaging, as a biomarker for human beta cell-derived cancers.