TY - JOUR T1 - <strong>First in human experience with [<sup>68</sup>Ga]P16-093, a novel Ga-68 labeled Prostate Specific Membrane Antigen (PSMA) inhibitor</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 52 LP - 52 VL - 59 IS - supplement 1 AU - Robert Doot AU - David Alexoff AU - Daniel Pryma AU - Kyle Labban AU - Erin Schubert AU - Matthew Fillare AU - Karl Ploessl AU - Seok Choi AU - Zhihao Zha AU - David Mankoff AU - Hank Kung Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/52.abstract N2 - 52Objectives: The Ga-68 labeled Glu-Urea-Lys(Ahx)-HBED-CC derivative [68Ga]P16-093 is being evaluated in Phase I clinical trials as a Positron Emission Tomography (PET) imaging agent targeting PSMA. Preclinical evaluation of [68Ga]P16-093 showed high and specific uptake in LNCap/PSMA+ cells and tumor-bearing mice. This study reports the first human biodistribution and kinetic data from prostate (PCa) and renal cell (RCC) cancer patients. Methods: [68Ga]P16-093, containing a novel linker between HBED-CC and Glu-Urea-Lys(Ahx) groups, was prepared by a custom automated synthesizer with a 68Ge/68Ga generator. Six confirmed cancer patients (2 RCC, 4 PCA) post primary treatment were administered [68Ga]P16-093 (130 - 190 MBq) and imaged on a Philips Ingenuity PET/CT for up to 3 hours. In 2 PCa patients with low/stable serum Prostate Specific Antigen (PSA), organ and body absorbed radiation doses were calculated from time-activity curves generated from regions of interest (ROI) drawn to encompass source organs. Total activity residing in the brain, heart contents, intestines, kidneys, liver, lungs, spleen, gallbladder, salivary glands, and urinary bladder were measured directly from PET images via Pmod v3.7 software (PMOD Technologies LLC). Activity in red marrow was calculated using activity concentrations in lumbar vertebrae 2-4. Urine counts were measured in a well counter. For time activity curves that were poorly fit by exponential functions, a Riemann Sum was used to calculate numbers of disintegrations occurring in organs. Dosimetry estimates were calculated using the Standard Adult Male phantom in OLINDA | EXM v1.1 software except for the absorbed dose in the salivary (parotid and submandibular) glands was calculated according to Herrmann et al. (JNM 2015; 56:855-861). Maximum standardized uptake values (SUVmax) were determined for normal organs for the dosimetry patients and for detected lesions in patients with metastatic disease. Results: [68Ga]P16-093 was consistently prepared by an in-house automated synthesizer with 80% final yield and &gt;90% purity. [68Ga]P16-093 PET images showed high uptake and retention in known PSMA-avid organs with rapid clearance from non-specific tissue and blood. Observed SUVmax for kidney, liver, spleen and parotid glands in the two dosimetry patients at ~ 60 min was 24.7 ± 7.0; 7.0 ± 0.1; 12.7 ± 2.9; 18.6 ± 2.8 g/mL respectively. Lesions were detected in RCC and PCa patients [SUVmax = 4.5 g/mL (RCC; lung), 6.2 g/mL (PCa; rib), 6.4 g/mL (RCC; pancreatic head)]. In the two PCa patients where dosimetry was calculated, the highest mean organ doses were: kidney (0.226 mSv/MBq); spleen (0.156 mSv/MBq); salivary glands (0.154 mSv/MBq) and small intestine (0.063 mSv/MBq). The effective dose was 0.021 mSv/MBq. These preliminary dosimetry data are in general agreement with published values for similar Ga-68 labeled PSMA inhibitors (68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline (EJNMMI 2017; 44(6):1014-24)). Conclusion: The results suggest that [68Ga]P16-093 may be suitable as a imaging agent for PSMA expression in cancer patents. Research Support: N/A ER -