Imaging of prostate cancer with immuno-PET and immuno-SPECT using a radiolabeled anti-EGP-1 monoclonal antibody.
ABSTRACT hRS7 is a humanized IgG1 monoclonal antibody directed against the epithelial glycoprotein-1 (EGP-1; also known as TROP2). This antigen is found in many epithelial cancers, including prostate cancer, and therefore this antibody could be suitable for targeting this cancer. In this study, the characteristics of hRS7 for targeting prostate cancer were examined. The potential for immuno-PET with (89)Zr-hRS7 and immuno-SPECT with (111)In-hRS7 was assessed using nude mice with human prostate cancer xenografts.
EGP-1 expression was assessed by immunohistology in human primary and metastatic prostate cancer samples and in PC3 xenografts. The optimal antibody protein dose for prostate cancer targeting was examined in nude mice with subcutaneous PC3 xenografts, and then the biodistribution of (111)In-, (125)I-, and (89)Zr-labeled hRS7 was determined in subcutaneous PC3 xenografts at 1, 3, and 7 d after injection. Immuno-PET and immuno-SPECT were performed with (89)Zr-hRS7 and (111)In-hRS7 in mice with subcutaneous and intraprostatic PC3 xenografts, respectively.
Immunohistochemical analysis showed abundant EGP-1 expression in human primary and metastatic prostate cancers and in PC3 xenografts. (111)In-hRS7 and (89)Zr-hRS7 preferentially and specifically accumulated in PC3 xenografts, with tumor uptake as high as 60% injected dose per gram at a protein dose of 0.1 μg per mouse. PC3 tumors in nude mice were clearly visualized with both tracers with immuno-PET and immuno-SPECT.
hRS7 shows excellent in vivo tumor targeting in human prostate cancer xenografts. Therefore, hRS7 is a potential vehicle for targeting prostate cancer.
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ABSTRACT: Identification of cancer cell-surface biomarkers and advances in antibody engineering have led to a sharp increase in the development of therapeutic antibodies. These same advances have led to a new generation of radiolabeled antibodies and antibody fragments that can be used as cancer-specific imaging agents, allowing quantitative imaging of cell-surface protein expression in vivo. Immuno-positron emission tomography (immunoPET) imaging with intact antibodies has shown success clinically in diagnosing and staging cancer. Engineered antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) -Fc, have been successfully employed for immunoPET imaging of cancer cell-surface biomarkers in preclinical models and are poised to bring same-day imaging into clinical development. ImmunoPET can potentially provide a noninvasive approach for obtaining target-specific information useful for titrating doses for radioimmunotherapy, for patient risk stratification and selection of targeted therapies, for evaluating response to therapy, and for predicting adverse effects, thus contributing to the ongoing development of personalized cancer treatment.Journal of Clinical Oncology 09/2012; · 18.04 Impact Factor
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ABSTRACT: PURPOSE: TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2 Fab fragments and one anti-histamine-succinyl-glycine (HSG) Fab fragment. The TROP-2 antigen is found in many epithelial cancers, including prostate cancer (PC), and therefore this bispecific antibody could be suitable for pretargeting in this cancer. In this study, the characteristics and the potential for pretargeted radioimmunoimaging and radioimmunotherapy with TF12 and the radiolabeled di-HSG peptide IMP288 in mice with human PC were investigated. METHODS: The optimal TF12 protein dose, IMP288 peptide dose, and dose interval for PC targeting were assessed in nude mice with s.c. PC3 xenografts. Immuno-positron emission tomography (PET)/CT was performed using TF12/(68)Ga-IMP288 at optimized conditions. The potential of pretargeted radioimmunotherapy (PRIT) using the TF12 pretargeted (177)Lu-IMP288 was determined. RESULTS: TF12 and (111)In-IMP288 showed high and fast accumulation in the tumor [20.4 ± 0.6 %ID/g at 1 h post-injection (p.i.)] at optimized conditions, despite the internalizing properties of TF12. The potential for PRIT was shown by retention of 50 % of the (111)In-IMP288 in the tumor at 48 h p.i. One cycle of treatment with TF12 and (177)Lu-IMP288 showed significant improvement of survival compared to treatment with (177)Lu-IMP288 alone (90 vs. 67 days, p < 0.0001) with no renal or hematological toxicity. CONCLUSION: TROP-2-expressing PC can be pretargeted efficiently with TF12, with very rapid uptake of the radiolabeled hapten-peptide, IMP288, sensitive immuno-PET, and effective therapy.European Journal of Nuclear Medicine 05/2013; · 4.53 Impact Factor