Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen.
OBJECTIVE
We performed an interim analysis of imaging data collected in 2 phase I radioimmunotherapy trials to determine the ability of monoclonal antibody (mAb) J591 directed to the extracellular domain of prostate specific membrane antigen (PSMA) to target sites of known metastatic prostate cancer accurately.


METHODS
Patients with progressing hormone independent prostate cancer were entered in 2 phase I dose finding trials with radiolabeled mAb J591. J591 is the first mAb targeting the extracellular domain of PSMA as well as the first de-immunized (humanized) mAb to PSMA to be tested in humans. These trials were primarily designed to assess dose limiting toxicity, maximum tolerated dose, pharmacokinetics and organ dosimetry. Planar gamma camera imaging studies obtained on the first 53 patients were reviewed and compared to sites of metastatic prostate cancer visualized on conventional imaging studies including bone scan, computerized tomography and/or magnetic resonance imaging. In 1 trial 29 patients received 111indium-J591 for imaging followed by 90yttrium-J591 for therapy. In the parallel trial 24 patients were treated with 177lutetium-J591, an isotope that can be imaged directly.


RESULTS
Of 53 patients reviewed 46 (87%) had evidence of metastatic disease on conventional scans. Overall, of the 43 evaluable patients J591 accurately targeted bone and/or soft tissue lesions in 42 (98%). J591 accurately targeted bone lesions in 32 of 34 (94%) and soft tissue lesions in 13 of 18 (72%) evaluable patients.


CONCLUSIONS
Radiolabeled J591 accurately targets bone and soft tissue metastatic prostate cancer sites, and may be useful for targeting therapeutic and/or diagnostic imaging agents.
Bander
Neil H
NH
Department of Urology, Division of Nuclear Medicine, New York-Presbyterian Hospital/Weill Medical College of Cornell University, 525 East 68th Street, Starr 900, New York, NY 10021, USA. nhbander@med.cornell.edu
Trabulsi
Edouard J
EJ
Kostakoglu
Lale
L
Yao
Daniel
D
Vallabhajosula
Shankar
S
Smith-Jones
Peter
P
Joyce
Maureen A
MA
Milowsky
Matthew
M
Nanus
David M
DM
Goldsmith
Stanley J
SJ
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000000981:diagnostic imaging / Q000276:immunology; D015902:Gamma Cameras; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D011877:Radionuclide Imaging; D012680:Sensitivity and Specificity; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary*; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C478680:J591 monoclonal antibody; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II