Acidic extracellular pH is a prominent biomarker in various disease conditions such as cancer, inflammation, and infection. Thus, extracellular pH measurements provide important information regarding disease status and progression. Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging platform that can effectively probe extracellular pH with an exogenous contrast agent.  However, one of the current limitations of exogenous CEST agents is their relatively low sensitivity, typically requiring &gt;1 mM of agent for detection, and ~10 mM for precisely measuring pH. Many existing CEST agents suffer from low sensitivity due to their limited number of exchangeable protons as well as the small difference in exchangeable proton chemical shift with water. Conjugation of pH-sensitive CEST probe to a polymeric platform will increase the number of exchangeable protons in the agent. Dendrimers are well known, a versatile polymeric platform for drug and gene delivery.  Our focus was to develop a pH-sensitive dendritic CEST probe with highly shifted exchangeable protons. Salicylic acid (SA) conjugated dendrimer can generate two pH-dependent CEST signals at 5.0 and 9.2 ppm for amide and salicylic acid protons respectively. The ratiometric approach of these signals provides more accurate pH imaging acquisition with no concentration dependency.<br/>Poly(amidoamine) (PAMAM) dendrimers are extensively used in therapeutic and contrast agent development. There are 126 terminal amine groups are available in generation 5 (G5) amine-terminated PAMAM dendrimer for the conjugation. Thus, SA was conjugated to G5 amine-terminated PAMAM dendrimer. Based on the results obtained from <sup>1</sup>H-NMR and MALDI-TOF, 60 SA units were successfully conjugated to G5-dendrimer. Ongoing CEST MRI phantom studies for pH detection will be presented. <br/>

Ratiometric pH imaging with a dendritic CEST MRI contrast agent

2019 Fall National Meeting

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