SPECT/CT Imaging of Prostatic PSMA Expression with Tc99m trofolastat chloride in Healthy Volunteers

Objectives Tc-99m trofolastat chloride (MIP-1404) is an investigational small molecule ligand based on a glutamate-urea-lysine pharmacophore which binds to the external domain of PSMA and has utility in the imaging of prostate cancer (JNM 2014;55(11):1791-8). While an increasing number of studies using PSMA targeted imaging agents have focused on pathologic uptake, information related to normal uptake in specific organs such as the prostate is sparse. In this investigation, we report normal target-to-background (TBR) ratios of prostatic uptake using MIP-1404 in the prostate glands of healthy volunteers (HV).

Methods Healthy male volunteers between the ages of 40-60 years old without current evidence of prostate disease, a serum PSA value < 4 ng/mL, and prostate MRI with no evidence of cancer underwent pelvic SPECT/CT imaging 3-6 hours following the i.v. injection of 20 (±3) mCi of MIP-1404. Tomographic images were reconstructed and corrected for attenuation using iterative techniques. Two cm circular regions of interest (ROIs) were placed in the axial slice of the reconstructed SPECT scan demonstrating the maximal number of counts in the gland and over the obturator internus muscle for a local background value of mean counts. These values were used to derive a single maximal TBR for each subject. Mean and standard deviation were calculated for age, TBR and PSA. Two-sided confidence intervals were calculated using the approximated standard deviation and student’s t-distribution about the mean TBR.

Results 14 men with a mean age of 49.9 ± 6.0 years (range 41-59) were enrolled and imaged. Mean TBR measured in the prostate gland and local muscle was 10.9±2.9 (range 7.0-18.1, 95% CI 9.2-12.6). Serum PSA values averaged 0.99 ± 0.6 ng/mL on the day of imaging. No treatment- related adverse events were identified.

Conclusions Uptake of MIP-1404 in prostatic tissue of HV is consistently low, with a mean calculated TBR of 10.9±2.9. These values provide a frame of reference when evaluating pelvic MIP-1404 SPECT/CT scans (acquired and reconstructed using identical parameters) performed on prostate cancer patients undergoing evaluation in clinical trials (JNM 2014;55(suppl 1)15) where mean TBR has been reported to be 26:1 in histologically-proven disease.

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