Synthesis and evaluation of 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression
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Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941
Published on: April 28, 2019
Hiroyuki Tateishi1, Atsushi B Tsuji2, Koichi Kato3
1Experimental Nuclear Medicine Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Abstract:
Upregulated monocarboxylate transporters (MCTs) in tumors are considered diagnostic imaging targets. Herein, we synthesized the positron emission tomography probe candidates coumarin analogs 2 and 3, and showed 55 times higher affinity of 2 for MCTs than a representative MCT inhibitor. Whereas [11C]2 showed low tumor accumulation, probably due to adduct formation with plasma proteins, [11C]2 showed high initial brain uptake, suggesting that the scaffold of 2 has properties that are preferable in imaging probes for the astrocyte-neuron lactate shuttle. Although further optimization of 2 is required, our findings can be used to inform the development of MCT-targeted imaging agents.
Insights
Researchers developed novel positron emission tomography (PET) imaging agents targeting monocarboxylate transporters (MCTs). While one agent showed high affinity for MCTs, further optimization is needed for effective tumor imaging.
Area of Science:
- Molecular Imaging
- Radiochemistry
- Oncology
Background:
- Monocarboxylate transporters (MCTs) are frequently upregulated in tumors, making them promising targets for diagnostic imaging.
- Developing specific and effective positron emission tomography (PET) probes is crucial for visualizing MCT expression in vivo.
Purpose of the Study:
- To synthesize and evaluate novel coumarin-based PET probe candidates targeting MCTs.
- To assess the affinity, tumor accumulation, and biodistribution of the synthesized probes for potential diagnostic applications.
Main Methods:
- Synthesis of coumarin analogs 2 and 3 as potential PET probe candidates.
- In vitro assessment of probe affinity for MCTs compared to a known inhibitor.
- In vivo evaluation of the radiolabeled probe [11C]2 using PET imaging to determine tumor and brain uptake.
Main Results:
- Coumarin analog 2 exhibited a 55-fold higher affinity for MCTs than a reference MCT inhibitor.
- The PET probe [11C]2 demonstrated low tumor accumulation, potentially due to plasma protein adduct formation.
- [11C]2 showed significant initial uptake in the brain, indicating suitability for astrocyte-neuron lactate shuttle imaging.
Conclusions:
- The coumarin scaffold shows promise for developing MCT-targeted imaging agents, particularly for brain applications.
- Further structural optimization of coumarin analog 2 is necessary to improve tumor targeting and overcome limitations like protein binding.
- These findings provide valuable insights for the future development of PET probes for MCT-driven diseases.
