RT Journal Article SR Electronic T1 First-in-Human Phase I study of CTT1057, a Novel 18F Labeled Imaging Agent with Phosphoramidate Core Targeting Prostate Specific Membrane Antigen in Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.118.220715 DO 10.2967/jnumed.118.220715 A1 Spencer C Behr A1 Rahul Aggarwal A1 Henry F. Van Brocklin A1 Robert R Flavell A1 Kenneth Geo A1 Eric J. Small A1 Joseph Blecha A1 Salma Jivan A1 Thomas A. Hope A1 Jeffrey P. Simko A1 John Kurhanewicz A1 Susan M. Noworolski A1 Natalie J. Korn A1 Romelyn De Los Santos A1 Matthew R. Cooperberg A1 Peter R Carroll A1 Hao G. Nguyen A1 Kirsten L. Greene A1 Beatrice Langton-Webster A1 Clifford E Berkman A1 Youngho Seo YR 2018 UL http://jnm.snmjournals.org/content/early/2018/11/20/jnumed.118.220715.abstract AB Prostate-specific membrane antigen (PSMA) targeting agents comprise a rapidly emerging class of radiopharmaceuticals for prostate cancer diagnostic imaging. 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-human Phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Methods: Two patient cohorts were recruited. Cohort A were patients with biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B were patients with metastatic castrate resistant prostate cancer. Cohort A patients were imaged on multiple time points after intravenous (IV) injection with 362 ± 8 MBq CTT1057 to evaluate the kinetics of CTT1057 and estimate radiation dose profiles. Mean organ-absorbed doses and effective doses were calculated using OLINDA. CTT1057 uptake in the prostate gland and regional lymph nodes was correlated with pathology, PSMA staining, and results of conventional imaging. In cohort B, patients were imaged 60 to 120 minutes after injection of CTT1057. PET images were assessed for overall image quality, and areas of abnormal uptake were contrasted with conventional imaging. Results: No radiotracer-related adverse events were reported in either cohort. Five patients were enrolled in cohort A and 15 in cohort B. In cohort A, the average total effective dose was 0.023 mSv/MBq. The kidneys exhibited the highest absorbed dose, 0.067 mGy/MBq. Absorbed doses of the liver, red marrow, and salivary glands were 0.016, 0.007, and 0.015 mGy/MBq, respectively. For cohort B, CTT1057 PET detected 97 metastatic lesions (median SUVmax: 12.17; IQR: 5.9 – 19.02). Of 56 bone metastases detected on CTT1057 PET, 44 (78.5%) were also detectable on whole body bone scan. Of 32 positive lymph nodes visualized on CTT1057 PET, 8 (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. CTT1057 detects metastatic lesions with higher sensitivity than conventional imaging. Further prospective studies with CTT1057 are warranted to eludicate its role in cancer imaging.