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

被引：3

作者：

Pekosak, Aleksandra ^{[1
]}

Bulc, Janez Z. ^{[1
]}

Korat, Spela ^{[1
]}

Schuit, Robert C. ^{[1
]}

Kooijman, Esther ^{[1
]}

Vos, Ricardo ^{[1
]}

Rongen, Marissa ^{[1
]}

Verlaan, Mariska ^{[1
]}

Takkenkamp, Kevin ^{[1
]}

Beaino, Wissam ^{[1
]}

Poot, Alex J. ^{[1
]}

Windhorst, Albert D. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, NL-1081 HV Amsterdam, Netherlands

来源：

MOLECULAR PHARMACEUTICS | 2018年 / 15卷 / 11期

关键词：

substance P1-7; CO2; fixation; carbon-11; metabolism; biodistribution; PET imaging; SP AMINOTERMINAL SP1-7; P; 1-7; HIGH-AFFINITY; BINDING-SITE; BRAIN; RECEPTORS; DISCOVERY; INTERACT; ANALOGS; NK1;

D O I：

10.1021/acs.molpharmaceut.8b00518

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Two potent SP1-7 peptidomimetics have been successfully radiolabeled via [C-11]CO2-fixation with excellent yields, purity, and molar activity. L-[C-11]SP1-7-peptidomimetic exhibited promising ex vivo biodistribution profile. Metabolite analysis showed that L-[C-11]SP1-7-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-[C-11]SP1-7-peptidomimetic. A slight decrease in SUV value was observed after pretreatment with natural peptide SP1-7 in spinal cord for L-[C-11]SP1-7-peptidomimetic. On the contrary, blocking using cold analogues of L- and D-[C-11]tracers did not reduce the tracers' brain and spinal cord exposure. In summary, PET scanning of L- and D-[C-11]SP1-7-peptidomimetics confirms rapid blood-brain barrier and blood-spinal-cord barrier penetration. Therefore, further validation of these two tracers targeting SP1-7 is needed in order to define a new PET imaging target and select its most appropriate radiopharmaceutical.

引用

页码：4872 / 4883

页数：12