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Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors
Neeta Pandit-Taskar1, Joseph A O'Donoghue2, Chaitanya R Divgi3
1Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Department of Radiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065 USA.
Background:
J591 is a monoclonal antibody that targets the external domain of the prostate-specific membrane antigen (PSMA). Besides prostate cancer cells, it also targets the neovasculature of non-prostate solid tumors. We provide an analysis of the antibody mass-dose dependency of lesion uptake and normal tissue retention, together with an assessment of lesion detectability using (111)In-J591 imaging, compared with conventional imaging in patients with a variety of solid tumors.
Methods:
Twenty patients in six cohorts received fixed amounts (5, 10, 20, 40, 60, and 100 mg) of J591 in a phase I trial. A maximum of four administrations per patient was given, with each administration separated by 3 weeks. All antibody administrations included 370 MBq (10 mCi) of (111)In labeled to 2 mg of J591 via the chelating agent DOTA. Three whole body (WB) gamma camera scans with at least one SPECT scan, along with multiple WB count-rate measurements and blood samples, were obtained for all patients. The effect of escalating antibody mass on lesion uptake and normal tissue retention was evaluated using lesion, liver, serum, and WB residence times and ratios thereof for each treatment cycle. Lesion detectability using (111)In-J591 imaging was compared to the standard imaging on a lesion-by-lesion basis.
Results:
A total of 170 lesions in 20 patients were detected by standard or (111)In-J591 imaging. (111)In-J591 targeted both skeletal and soft tissue diseases in all tumor types. (111)In-J591 imaging identified 74% (20/27) of skeletal lesions, 53% (18/34) of nodes, and 64% (70/109) of other soft tissue/organ lesions. There was increasing (111)In-J591 uptake in lesions with increasing antibody mass-dose, coupled with decreasing retention in the liver for increments up to 20 mg, and no significant change at higher antibody mass.
Conclusions:
Radiolabeled J591 antibody has potential as a targeting agent for solid tumor vasculature and lesion detection. Bone and soft tissue lesions arising from tumors of diverse origin were targeted by the anti-PSMA antibody J591. For the detection of lesions in these tumors by J591 antibody scans, an antibody mass of 20 mg is adequate. The optimal time of imaging is 5 to 7 days post-injection.
Insights
Radiolabeled J591 antibody effectively targets solid tumor vasculature and detects lesions across various cancer types. An antibody mass of 20 mg is sufficient for optimal lesion detection, with imaging best performed 5-7 days post-injection.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Immunotherapy
Background:
- J591 is a monoclonal antibody targeting prostate-specific membrane antigen (PSMA) on prostate cancer cells and tumor neovasculature.
- It shows potential for targeting non-prostate solid tumors.
- This study analyzes J591's mass-dose effects on lesion uptake and retention.
Purpose of the Study:
- To evaluate the antibody mass-dose dependency of lesion uptake and normal tissue retention for (111)In-J591.
- To assess lesion detectability using (111)In-J591 imaging compared to conventional methods.
- To determine the optimal antibody mass and imaging time for J591-based tumor detection.
Main Methods:
- A Phase I trial involving 20 patients in six cohorts receiving 5-100 mg of J591.
- (111)In-labeled J591 (2 mg) was administered with escalating antibody masses.
- Whole body gamma camera scans, SPECT scans, and blood samples were collected to evaluate uptake, retention, and detectability.
Main Results:
- A total of 170 lesions were detected across diverse tumor types.
- (111)In-J591 imaging identified 74% of skeletal lesions, 53% of nodal lesions, and 64% of other soft tissue/organ lesions.
- Increasing antibody mass up to 20 mg enhanced lesion uptake and decreased liver retention.
Conclusions:
- Radiolabeled J591 is a promising agent for solid tumor vasculature targeting and lesion detection.
- An antibody mass of 20 mg is adequate for detecting bone and soft tissue lesions in various tumors.
- Optimal imaging time for J591 antibody scans is 5 to 7 days post-injection.
