2. Academic Validation
  3. C-terminal-modified LY2510924: a versatile scaffold for targeting C-X-C chemokine receptor type 4

C-terminal-modified LY2510924: a versatile scaffold for targeting C-X-C chemokine receptor type 4

  • Sci Rep. 2019 Oct 25;9(1):15284. doi: 10.1038/s41598-019-51754-0.
Kentaro Suzuki 1 2,  Takashi Ui 3,  Akio Nagano 4,  Akihiro Hino 4,  Yasushi Arano 5
Affiliations

Affiliations

  • 1 RI Research Department, Research Division, FUJIFILM Toyama Chemical Co., Ltd., 453-1, Shimo-Okura, Matsuo-Machi, Sammu-City, Chiba, 289-1592, Japan. kentaro.a.suzuki@fujifilm.com.
  • 2 Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8675, Japan. kentaro.a.suzuki@fujifilm.com.
  • 3 Research Department, FUJIFILM RI Pharma Co., Ltd., 453-1, Shimo-Okura, Matsuo-Machi, Sammu-City, Chiba, 289-1592, Japan.
  • 4 RI Research Department, Research Division, FUJIFILM Toyama Chemical Co., Ltd., 453-1, Shimo-Okura, Matsuo-Machi, Sammu-City, Chiba, 289-1592, Japan.
  • 5 Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8675, Japan.
PMID: 31653903 DOI: 10.1038/s41598-019-51754-0
Abstract

C-X-C Chemokine Receptor type 4 (CXCR4) constitutes a promising target for tumor diagnosis and therapy. Herein, we evaluate a new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CXCR4 Antagonist derived from LY2510924, FRM001, and its metal complexes as CXCR4-targeting probes. FRM001 was synthesized by modifying the C-terminus of LY2510924 with maleimido-mono-amide-DOTA via a cysteine linker. FRM001 exhibited CXCR4-specific binding with an affinity similar to that of the parental LY2510924. The binding affinity of FRM001 remained unchanged after complexation with Ga, Lu, and Y. The internalization of 67Ga-FRM001 into the cells was hardly observed. In mice biodistribution studies, 67Ga-FRM001 exhibited high accumulation in the tumor and the liver with rapid elimination rates from the blood. The hepatic accumulation of 67Ga-FRM001 was preferentially and significantly reduced by co-injecting a CXCR4 Antagonist, AMD3100. The C-terminal-modified LY2510924 would constitute a versatile scaffold to develop CXCR4-targeting probes or therapeutics for tumor imaging or therapy.

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