99m Tc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of 99m Tc-EDDA/HYNIC-iPSMA (99m Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients.

METHODS: 99m Tc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after 99m Tc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the 99m Tc-EDDA/HYNIC-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h.

RESULTS: The blood activity showed a half-life value of 4.98min for the fast component (T1/2 α=ln2/8.34), 2.49h for the first slow component (T1/2 β=ln2/0.278), and 9.24h for the second slow component (T1/2 γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv.

CONCLUSIONS: All the absorbed doses were comparable to those known for most of the 99m Tc studies. 99m Tc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical to target site-specific prostate cancer.