@article {Behrjnumed.118.220715, author = {Spencer C Behr and Rahul Aggarwal and Henry F. Van Brocklin and Robert R Flavell and Kenneth Geo and Eric J. Small and Joseph Blecha and Salma Jivan and Thomas A. Hope and Jeffrey P. Simko and John Kurhanewicz and Susan M. Noworolski and Natalie J. Korn and Romelyn De Los Santos and Matthew R. Cooperberg and Peter R Carroll and Hao G. Nguyen and Kirsten L. Greene and Beatrice Langton-Webster and Clifford E Berkman and Youngho Seo}, title = {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}, elocation-id = {jnumed.118.220715}, year = {2018}, doi = {10.2967/jnumed.118.220715}, publisher = {Society of Nuclear Medicine}, abstract = {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 {\textpm} 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 {\textendash} 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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/early/2018/11/20/jnumed.118.220715}, eprint = {https://jnm.snmjournals.org/content/early/2018/11/20/jnumed.118.220715.full.pdf}, journal = {Journal of Nuclear Medicine} }