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Abstract

PURPOSE:

Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of (89)Zr-DFO-huJ591 ((89)Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology.

EXPERIMENTAL DESIGN:

Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of (89)Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites.

RESULTS:

Median standardized uptake value for (89)Zr-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). (89)Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, (89)Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 (89)Zr-J591-positive osseous sites and 14 of 16 (89)Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of (89)Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions.

CONCLUSIONS:

(89)Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although (89)Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer. Clin Cancer Res; 21(23); 5277-85.  

Author information

Pandit-Taskar N1, O'Donoghue JA2, Durack JC3, Lyashchenko SK4, Cheal SM5, Beylergil V3, Lefkowitz RA6, Carrasquillo JA6, Martinez DF7, Fung AM3, Solomon SB6, Gönen M8, Heller G8, Loda M9, Nanus DM10, Tagawa ST10, Feldman JL7, Osborne JR6, Lewis JS11, Reuter VE12, Weber WA6, Bander NH13, Scher HI14, Larson SM15, Morris MJ14.​

1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York. pandit-n@mskcc.org.

2Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.

3Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

4Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York. Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.

5Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.

6Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York.

7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

8Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

9Department of Pathology, Dana-Farber Cancer Institute; Brigham & Women's Hospital; and Broad Institute, Boston, Massachusetts.

10Department of Medicine, Weill Cornell Medical College, New York, New York.

11Department of Radiology, Weill Cornell Medical College, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York. Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York.

12Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

13Department of Medicine, Weill Cornell Medical College, New York, New York. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

14Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.

15Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Radiology, Weill Cornell Medical College, New York, New York. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.