Radioligand Therapy of Prostate Cancer with a Long-lasting PSMA Targeting Agent 90Y-DOTA-EB-MCG

Zhantong Wang, Orit Jacobson, Rui Tian, Ronnie Mease, Dale Kiesewetter, Gang Niu, Martin Gilbert Pomper, Xiaoyuan Chen

Research output: Contribution to journalArticle


Several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for the treatment of prostate cancer. Among them, (((R)-1-carboxy-2-mcercaptoethyl)carbamoyl)-L-glutamic acid (MCG) has been successfully labeled with radioisotopes for prostate cancer imaging. The aim of this study is to conjugate MCG with an albumin binding moiety to further improve the in vivo pharmacokinetics. Methods: MCG was conjugated with an Evans blue (EB) derivative for albumin binding and a DOTA chelator. PSMA positive (PC3-PIP) and PSMA negative (PC3) cells were used for both in vitro and in vivo studies. Longitudinal PET imaging was performed at 1, 4, 24, and 48 h post injection to evaluate the biodistribution and tumor uptake of 86Y-DOTA-EB-MCG. DOTA-EB-MCG was also labeled with 90Y for radionuclide therapy. Besides tumor growth measurement, tumor response to escalating therapeutic doses were also evaluated by immunohistochemistry and fluorescence microscopy. Results: Based on quantification from 86Y-DOTA-EB-MCG PET images, the tracer uptake in PC3-PIP tumors increased from 22.33 ± 2.39 %ID/g at 1 h post-injection (p.i.), to the peak of 40.40 ± 4.79 %ID/g at 24 h p.i. Administration of 7.4 MBq of 90Y-DOTA-EB-MCG resulted in significant regression of tumor growth in PSMA positive xenografts. No apparent toxicity or body weight loss was observed in all treated mice. Conclusion: Modification of MCG with an Evans blue derivative resulted in a highly efficient prostate cancer targeting agent (EB-MCG), which showed great potential in prostate cancer treatment after being labeled with therapeutic radioisotopes.

Original languageEnglish (US)
JournalBioconjugate Chemistry
StateAccepted/In press - Apr 27 2018


ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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