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Two potent SP 1-7 peptidomimetics have been successfully radiolabeled via [ 11 C]CO 2 -fixation with excellent yields, purity, and molar activity. l-[ 11 C]SP 1-7 -peptidomimetic exhibited promising ex vivo biodistribution profile. Metabolite analysis showed that l-[ 11 C]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-[ 11 C]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-[ 11 C]SP 1-7 -peptidomimetic. On the contrary, blocking using cold analogues of l- and d-[ 11 C]tracers did not reduce the tracers' brain and spinal cord exposure. In summary, PET scanning of l- and d-[ 11 C]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.

Synthesis and Preclinical Evaluation of the First Carbon-11 Labeled PET Tracers Targeting Substance P1–7

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