Phase I Study of CTT1057, an 18F-Labeled Imaging Agent with Phosphoramidate Core Targeting Prostate-Specific Membrane Antigen in Prostate Cancer

J Nucl Med. 2019 Jul;60(7):910-916. doi: 10.2967/jnumed.118.220715. Epub 2018 Nov 21.


Agents targeting prostate-specific membrane antigen (PSMA) comprise a rapidly emerging class of radiopharmaceuticals for diagnostic imaging of prostate cancer. Unlike most other PSMA agents with a urea backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-humans phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Methods: Two patient cohorts were recruited. Cohort A patients had biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B patients had metastatic castration-resistant prostate cancer. Cohort A patients were imaged at multiple time points after intravenous injection with 362 ± 8 MBq of CTT1057 to evaluate the kinetics of CTT1057 and estimate radiation dose profiles. Mean organ-absorbed doses and effective doses were calculated. CTT1057 uptake in the prostate gland and regional lymph nodes was correlated with pathology, PSMA staining, and the results of conventional imaging. In cohort B, patients were imaged 60-120 min after injection of CTT1057. PET images were assessed for overall image quality, and areas of abnormal uptake were contrasted with conventional imaging. Results: In cohort A (n = 5), the average total effective dose was 0.023 mSv/MBq. The kidneys exhibited the highest absorbed dose, 0.067 mGy/MBq. The absorbed dose of the salivary glands was 0.015 mGy/MBq. For cohort B (n = 15), CTT1057 PET detected 97 metastatic lesions, and 44 of 56 bone metastases detected on CTT1057 PET (78.5%) were also detectable on bone scanning. Eight of 32 lymph nodes positive on CTT1057 PET (25%) were enlarged by size criteria on CT. Conclusion: CTT1057 is a promising novel phosphoramidate PSMA-targeting 18F-labeled PET radiopharmaceutical that demonstrates similar biodistribution to urea-based PSMA-targeted agents, with lower exposure to the kidneys and salivary glands. Metastatic lesions are detected with higher sensitivity on CTT1057 imaging than on conventional imaging. Further prospective studies with CTT1057 are warranted to elucidate its role in cancer imaging.

Keywords: CTT1057; PET; PSMA; dosimetry; prostate cancer.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Amides / adverse effects
  • Amides / chemistry*
  • Amides / metabolism*
  • Amides / pharmacokinetics
  • Antigens, Surface / metabolism*
  • Cohort Studies
  • Fluorine Radioisotopes*
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Isotope Labeling
  • Male
  • Middle Aged
  • Phosphoric Acids / adverse effects
  • Phosphoric Acids / chemistry*
  • Phosphoric Acids / metabolism*
  • Phosphoric Acids / pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Prospective Studies
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism*
  • Safety
  • Tissue Distribution
  • Whole Body Imaging


  • Amides
  • Antigens, Surface
  • Fluorine Radioisotopes
  • Phosphoric Acids
  • phosphoramidic acid
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Fluorine-18