Towards medical imaging of drug photoactivation:Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents  

作　　者：Ilse M.Welleman Carlijn L.F.van Beek Ioana Belcin Albert M.Schulte Rudi A.J.O.Dierckx Ben L.Feringa Hendrikus H.Boersma Wiktor Szymański 

机构地区：[1]Department of Radiology,Medical Imaging Center,University Medical Center Groningen,University of Groningen,Groningen,The Netherlands [2]Stratingh Institute for Chemistry,University of Groningen,Groningen,The Netherlands [3]Department of Clinical Pharmacy and Pharmacology,Nuclear Medicine and Molecular Imaging,University Medical Center Groningen,University of Groningen,Groningen,The Netherlands

出　　处：《Smart Molecules》2024年第2期129-138,共10页智能分子（英文）

摘　　要：In recent years,the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology.One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups(PPGs).To effectively utilize light-activated drugs in future medical applications,physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents.Here,we describe the development and evaluation of magnetic resonance(MR)imaging agents that allow for the detection of light penetration and drug activation in the tissues using non-invasive whole-body magnetic resonance imaging(MRI)and chemical exchange saturation transfer(CEST)-MRI modalities.The approach relies on the use of PPG-protected MR contrast agents,which upon irradiation with light change their imaging signal.A Gadolinium(III)-based MRI contrast agent is presented that undergoes a significant change in relaxivity(25%)upon uncaging,providing a reliable indicator of lightinduced cargo release.Additionally,we introduce the first light-responsive CESTMRI imaging agent,enabling positive signal enhancement(off-to-on)upon light activation,offering a novel approach to visualize the activation of photoactive agents in living tissues.This research provides a proof-of-principle for the noninvasive,whole-body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

关 键 词：CEST MRI PHOTOCHEMISTRY photocleavable protecting groups photopharmacology 

分 类 号：R73[医药卫生—肿瘤]