RT Journal Article SR Electronic T1 Phase I Study of CTT1057, an 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 910 OP 916 DO 10.2967/jnumed.118.220715 VO 60 IS 7 A1 Spencer C. Behr A1 Rahul Aggarwal A1 Henry F. VanBrocklin A1 Robert R. Flavell A1 Kenneth Gao A1 Eric J. Small A1 Joseph Blecha A1 Salma Jivan A1 Thomas A. Hope A1 Jeffry 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 2019 UL http://jnm.snmjournals.org/content/60/7/910.abstract AB 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.