Te Whakawhanaketanga o te Peptide Ligand Irerangi e kore e taea te whakahuri mo te whakaahua PET o te Waahanga Whakatupu Endothelial Vascular

Ko nga maataki whakaahua i runga i nga rangahau peptide he tino pai nga ahuatanga pharmacokinetic mena he hononga nui to raatau mo o raatau whaainga i roto i te vivo. Ko tetahi huarahi ki te whakapai ake i te hononga o te peptide ligand mo tana whaainga ko te hanga i tenei tauwhitinga kia noho tahi me te kore e taea te huri.. Mo tenei kaupapa, i arotakehia e matou he tohu peptide hononga 64Cu-tapanga, 64Cu-L19K-(5-fluoro-2,4-dinitrobenzene) (64Cu-L19K-FDNB), e herea ana me te korekore ki te tauwehe tipu endothelial vascular (VEGF) hei kaihoko whakaahua PET. I whakatairitehia e matou nga taonga in vivo o 64Cu-L19K-FDNB i roto i nga xenografts puku e whakaatu ana i te VEGF me ona tairitenga herenga kore-kore., 64Cu-L19K-(2,4-dinitrophenyl) (64Cu-L19K-DNP) me te 64Cu-L19K. Nga tikanga: Ko te peptide L19K (GGNECDIARMWEWECFERK-CONH2) i hangaia ki te waikawa 1,4,7-triazacyclononane-1,4,7-triacetic i te pito N mo te tapanga reo irirangi me te 64Cu me te mokowhiti polyethylene glycol i waenga i te peptide me te chelate.. 1,5-Ko te difluoro-2,4-dinitrobenzene i honoa ki te C-terminal lysine mo te hono whakawhiti ki te VEGF, ka puta ko L19K-FDNB. 64I whakamatauria a Cu-L19K-FDNB mo te herenga o te kovalent ki te VEGF in vitro. Hei mana whakahaere, I honoa a L19K ki te 1-fluoro-2,4-dinitrobenzene, ka puta ko L19K-DNP. PET atahanga me te rangahau biodistribution o 64Cu-L19K-FDNB, 64Cu-L19K-DNP, me te 64Cu-L19K taketake i whakaritea i roto i te HCT-116 xenografts. Ko nga rangahau aukati mo te 64Cu-L19K-FDNB i mahia me te whakakotahitanga o te taikaha L19K-FDNB kore tapanga.. Hua: Ko nga rangahau here in vitro i whakapumau i te here o te 64Cu-L19K-FDNB ki te VEGF., ko te 64Cu-L19K-DNP me te 64Cu-L19K karekau i herea. I whakaatuhia e te whakaahua PET te tango i te puku nui ake me te 64Cu-L19K-FDNB i te 64Cu-L19K-DNP me te 64Cu-L19K, me te tikanga o nga uara tango paerewa o 0.62 ± 0.05, 0.18 ± 0.06, a 0.34 ± 0.14, ia, i 24 h i muri i te werohanga (P < 0.05), a 0.53 ± 0.05, 0.32 ± 0.14, a 0.30 ± 0.09, ia, i 48 h i muri i te werohanga (P < 0.05). Ko te aukati i nga rangahau me te 64Cu-L19K-FDNB i te aroaro o te taikaha peptide kore tapanga i whakaatu he 53% te whakaiti i te tango i te puku i 48 h i muri i te werohanga. Whakamutunga: I roto i tenei rangahau tohu-a-arii, Ko te whakamahi i te herenga peptide herea ki te VEGF ka pai ake te whakaemi o nga kaiwhaiwhai i te waahi puku i roto i te vivo, whakaritea ki ona tairitenga peptide here kore-kovalent. Ko tenei tikanga he taputapu pai ki te whakarei ake i te kaha o nga rangahau peptide hei tohu whakaahua.