Molecular imaging for localized prostate cancer: Analysis of 2 prospective phase 0 trials of PSMA targeted immuno-pet and-SPECT, and implications for the radiation oncologist

  • D.E. S
  • S. F
  • S. L
 et al. 
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Abstract

Purpose/Objective(s): To report the efficacy and utility of PSMA-based molecular targeted imaging in localized prostate cancer using 111In-J591 SPECT and 89Zr-J591 immuno-PET. Materials/Methods: Initiated in 2010, two sequential phase 0 prospective studies were performed on a total of 19 patients evaluating the roles of 111In-J591 SPECT and 89Zr-J591 immuno-PET. All patients had a baseline MRI followed by a preoperative 111In-J591 SPECT or 89Zr- J591 PET scan. Patients subsequently underwent radical prostatectomy with immediate imaging of the ex vivo specimens with micro-SPECT or micro-PET/CT. For the 89Zr-J591 trial, the ex vivo specimens were also imaged with a custom MRI solenoid coil insert for higher resolution imaging. Findings on MRI and histopathology from the surgical specimen were compared to the pre-surgical molecular imaging and ex vivo images. Results: The 111In-J591 SPECT: Eight patients were enrolled with a median age of 64 years. Median pre-treatment PSA was 6.8 ng/mL (2.8- 22.7), and the median biopsy Gleason score was 7 (6-9). As SPECT imaging has limited lesion discriminatory power of detection, prostatectomy specimens were analyzed by the dominant tumor foci. The median pathologic Gleason score was 7 (7-9), and the median dominant lesion size was 9.5 mm (3-19 mm). Tumor was visible by MRI on 7 of the 8 patients, and was positive in all SPECT scans that correlated well to the prostatectomy specimen. One patient had positive lymph nodes on histopathology, but was negative by both MRI and SPECT. 89Zr-J591 PET: Eleven patients were enrolled with a median age of 61.0 years. Median pre-treatment PSA was 5.2 ng/mL (3.5-12.0), and the median biopsy Gleason score was 7 (7- 9). Twenty-two lesions were identified on histopathology. The median lesion size was 5.5 mm (2-21 mm), and the median pathologic Gleason score was 7 (6-9). Immuno-PET identification improved with increasing tumor size, and was true for both in vivo PET (P < 0.0001) and micro-PET (P < 0.0001). Furthermore, immuno-PET lesion identification improved with increasing Gleason score (for ex vivo micro-PET imaging, P = 0.01; in vivo imaging, P = 0.14). Lesions of Gleason score 3 + 3 = 6 were uniformly not detected by PET (0 of 14 lesions). Conclusions: Targeted molecular PSMA imaging using the monoclonal antibody J591 has the ability to detect clinically significant localized prostate cancer. The 89Zr-J591 PET has improved accuracy over 111In- J591 SPECT to detect isolated intraprostatic foci, likely secondary to inherent SPECT resolution limits. Clinically significant disease (Gleason score ≥7) was readily detected by immuno-PET, and may potentially serve as a non-invasive means for active surveillance monitoring. Based on the success of these preliminary studies, we are initiating a phase 2 immuno-PET/MRI study to further evaluate the multitude of uses of one of the first successful molecular imaging agents in localized prostate cancer.

Author-supplied keywords

  • Gleason score
  • biopsy
  • ex vivo study
  • histopathology
  • human
  • imaging
  • indium 111
  • lymph node
  • male
  • molecular imaging
  • monitoring
  • monoclonal antibody
  • monoclonal antibody J591
  • neoplasm
  • nuclear magnetic resonance imaging
  • oncology
  • patient
  • pet animal
  • positron emission tomography
  • prospective study
  • prostate cancer
  • prostatectomy
  • radiation oncologist
  • single photon emission computer tomography
  • society
  • tumor volume

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Authors

  • Spratt D.E.

  • Fareedy S.

  • Lindgren S.

  • Robinson B.

  • Larson S.M.

  • Lewis J.

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