Synthesis and Preclinical Evaluation of the First Carbon-11 Labeled PET Tracers Targeting Substance P_1-7.

ABSTRACT: Two potent SP_1-7 peptidomimetics have been successfully radiolabeled via [¹¹C]CO₂-fixation with excellent yields, purity, and molar activity. l-[¹¹C]SP_1-7-peptidomimetic exhibited promising ex vivo biodistribution profile. Metabolite analysis showed that l-[¹¹C]SP_1-7-peptidomimetic is stable in brain and spinal cord, whereas rapid metabolic degradation occurs in rat plasma. Metabolic stability can be significantly improved by substituting l-Phe for d-Phe, preserving 70% more of intact tracer and resulting in better brain and spinal cord tracer retention. Positron emission tomography (PET) scanning confirmed moderate brain (1.5 SUV; peak at 3 min) and spinal cord (1.0 SUV; peak at 10 min) uptake for l- and d-[¹¹C]SP_1-7-peptidomimetic. A slight decrease in SUV value was observed after pretreatment with natural peptide SP_1-7 in spinal cord for l-[¹¹C]SP_1-7-peptidomimetic. On the contrary, blocking using cold analogues of l- and d-[¹¹C]tracers did not reduce the tracers' brain and spinal cord exposure. In summary, PET scanning of l- and d-[¹¹C]SP_1-7-peptidomimetics confirms rapid blood-brain barrier and blood-spinal-cord barrier penetration. Therefore, further validation of these two tracers targeting SP_1-7 is needed in order to define a new PET imaging target and select its most appropriate radiopharmaceutical.

SUBMITTER: Pekosak A 

PROVIDER: S-EPMC6220361 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature