One-Step 18 F-Labeling and Preclinical Evaluation of Prostate-Specific Membrane Antigen Trifluoroborate Probes for Cancer Imaging

J Nucl Med. 2019 Aug;60(8):1160-1166. doi: 10.2967/jnumed.118.216598. Epub 2019 Feb 8.


After the identification of the high-affinity glutamate-ureido scaffold, the design of several potent 18F- and 68Ga-labeled tracers has allowed spectacular progress in imaging recurrent prostate cancer by targeting the prostate-specific membrane antigen (PSMA). We evaluated a series of PSMA-targeting probes that are 18F-labeled in a single step for PET imaging of prostate cancer. Methods: We prepared 8 trifluoroborate constructs for prostate cancer imaging, to study the influence of the linker and the trifluoroborate prosthetic on pharmacokinetics and image quality. After 1-step labeling by 19F-18F isotopic exchange, the radiotracers were injected in mice bearing LNCaP xenografts, with or without blocking controls, to assess specific uptake. PET/CT images and biodistribution data were acquired at 1 h after injection and compared with 18F-DCFPyL on the same mouse strain and tumor model. Results: All tracers exhibited nanomolar affinities, were labeled in good radiochemical yields at high molar activities, and exhibited high tumor uptake in LNCaP xenografts with clearance from nontarget organs. Most derivatives with a naphthylalanine linker showed significant gastrointestinal excretion. A radiotracer incorporating this linker with a dual trifluoroborate-glutamate labeling moiety showed high tumor uptake, low background activity, and no liver or gastrointestinal track accumulation. Conclusion: PSMA-targeting probes with trifluoroborate prosthetic groups represent promising candidates for prostate cancer imaging because of facile labeling while affording high tumor uptake values and contrast ratios that are similar to those obtained with 18F-DCFPyL.

Keywords: 18F labeling; 18F-trifluoroborate; PSMA; positron emission tomography; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / analysis*
  • Binding, Competitive
  • Borates / chemistry*
  • Cell Line, Tumor
  • Fluorine Radioisotopes / chemistry*
  • Glutamate Carboxypeptidase II / analysis*
  • Humans
  • Male
  • Mice
  • Neoplasm Recurrence, Local
  • Neoplasm Transplantation
  • Positron Emission Tomography Computed Tomography*
  • Prostate / diagnostic imaging
  • Prostatic Neoplasms / diagnostic imaging*
  • Radiopharmaceuticals / pharmacology*
  • Tissue Distribution


  • Antigens, Surface
  • Borates
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II