Abstract #1152

Dynamic CEST Imaging of Extracellular Lactate In Vivo in Subcutaneous Tumors using PARACEST Shift Reagents

Remy Chiaffarelli^1,2,3, Pedro F. Cruz⁴, Jonathan Cotton^1,2, Tjark Kelm¹, Slade Lee⁵, Mohammad Ghaderian^1,2,3, Max Zimmermann^1,2,3, Carlos F. G. C. Geraldes^4,6,7, Paul Jurek⁵, and André Martins^1,2,3

¹Werner Siemens Imaging Center, University Hospital Tuebingen, Tuebingen, Germany, ²Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tuebingen, Germany, ³German Cancer Consortium (DKTK), partner site Tübingen, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Coimbra Chemistry Center-Institute of Molecular Sciences (CQC-IMS), Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal, ⁵Macrocyclics, Inc., Plano, TX, United States, ⁶CIBIT—Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal, ⁷Department of Life Sciences, University of Coimbra, Coimbra, Portugal

Synopsis

Keywords: Probes & Targets, Contrast Agents, cest, paracest, lactate, cancer metabolism

Motivation: Lactate accumulation in the tumor microenvironment is a hallmark of cancer aggressiveness.

Goal(s): Non-invasive imaging of extracellular lactate in tumor models.

Approach: In vitro characterization of Eu- and Yb-PCTA as PARACEST shift reagents (SRs) and in vivo dynamic CEST MRI.

Results: The SRs shift the lactate OH-CEST signal away from the water signal by 14 ppm (EuPCTA) and 109 ppm (YbPCTA), allowing for selective detection of lactate excreted by cancer cells. In vivo experiments confirmed the detection and fast renal elimination of the lactate*YbPCTA into the bladder and the detection of extracellular lactate in MC-38 tumors by dynamic CEST MRI.

Impact: EuPCTA and YbPCTA enable selective imaging of extracellular lactate, allowing detection of metabolic compartments in the tumor microenvironment. PCTA-based complexes represent a scaffold for the optimization of metabolic responsive imaging probes to map tumor heterogeneity and aggressiveness.

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