Application of <sup>99m</sup>Tc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma

Otsuji, Eigo; Matsumura, Hiroomi; Okamoto, Kazuma; Toma, Atsushi; Kuriu, Yoshiaki; Ichikawa, Daisuke; Hagiwara, Akeo; Yamagishi, Hisakazu

doi:10.1002/jso.10311

Cited by 4 publications

(3 citation statements)

References 26 publications

(26 reference statements)

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“…While previous studies showed promising results, this study revealed the insufficient accumulation of the antibody-based probe in tumor tissue. However, a similar study successfully utilized a novel full and fragmented antibody (A7) labeled with 125 I and 99m Tc for imaging of nude mice bearing human pancreatic cancer subcutaneous xenograft tumors. , The ratio of radioactivity in tumor tissue, as compared to blood, was significantly higher than that in normal tissue, with the full antibody displaying higher tumor uptake as compared to the antibody fragment.…”

Section: Molecular Imaging Of Pancreatic Cancermentioning

confidence: 99%

Molecular Imaging of Pancreatic Cancer with Antibodies

et al. 2015

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Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine.

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Section: Molecular Imaging Of Pancreatic Cancermentioning

confidence: 99%

Molecular Imaging of Pancreatic Cancer with Antibodies

et al. 2015

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“…Then, the effect of treatment with the 131 I-labeled chimeric anti-VEGFR2 Fab was determined. To our knowledge, these observations were seldom made in previous studies 19 42 43 that reported the anti-tumor role of radionuclide labeled mAbs.…”

Section: Discussionmentioning

confidence: 77%

Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

Huang

Tang

Wang

et al. 2015

Sci Rep

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Vascular endothelial growth factor receptor 2 (VEGFR2) is traditionally regarded as an important therapeutic target in a wide variety of malignancies, such as hepatocellular carcinoma (HCC). We previously generated a murine-human anti-VEGFR2 chimeric Fab (cFab), named FA8H1, which has the potential to treat VEGFR2-overexpressing solid tumors. Here, we investigated whether FA8H1 can be used as a carrier in molecularly targeted therapy in HCC xenograft models. FA8H1 was labeled with 131I, and two HCC xenograft models were generated using BEL-7402 (high VEGFR2-expressing) and SMMC-7721 (low VEGFR2-expressing) cells, which were selected from five HCC cell lines. The biodistribution of 131I-FA8H1 was determined in both models by Single-Photon Emission Computed Tomography and therapeutic effects were monitored in nude mice bearing BEL-7402 xenografts. Finally, we determined the involvement of necrosis and apoptotic pathways in treated mice using immunohistochemistry. 131I-FA8H1 levels were dramatically reduced in blood and other viscera. The therapeutic effect of 131I-labeled FA8H1 in the BEL-7402 model was significantly better than that by 131I and FA8H1 alone. We observed extensive necrosis in the treated tumors, and both FasL and caspase 3 were up-regulated. Thus, 131I-anti-VEGFR2 cFab has the potential to be used for molecularly targeted treatment of HCC overexpressing VEGFR2.

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“…Others have also examined the application of mAbs to target and provide in vivo imaging of pancreatic cancers, mostly as xenografts in athymic nude mice, although a few have been studied in clinical trials as well (31)(32)(33)(34)(35). While it is difficult to compare all of these previous studies, for the most part radiolabeled whole-IgG has been used, with the result that the highest tumor/blood ratios occurred between 72 and 96 hours postinjection and were in the range of 2:1 to 10:1; in other words, similar to the results we obtained with radiolabeled PAM4 whole-IgG.…”

Section: Discussionmentioning

confidence: 99%

A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma

et al. 2008

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Preclinical and clinical studies have demonstrated the application of radiolabeled mAb-PAM4 for nuclear imaging and radioimmunotherapy of pancreatic carcinoma. We have now examined the ability of a novel PAM4-based, bispecific monoclonal antibody (mAb) construct, TF10, to pretarget a radiolabeled peptide for improved imaging and therapy. TF10 is a humanized, bispecific mAb, divalent for mAb-PAM4 and monovalent for mAb-679, reactive against the histaminesuccinyl-glycine hapten. Biodistribution studies and nuclear imaging of the radiolabeled TF10 and/or TF10-pretargeted hapten-peptide (IMP-288) were conducted in nude mice bearing CaPan1 human pancreatic cancer xenografts.125

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Application of ^99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma

Abstract: Because the half-life of (99m)Tc is short (6 hr), chA7Fab, which accumulates rapidly in tumors, may be a better carrier of (99m)Tc than intact Mab A7.

Cited by 4 publications

References 26 publications

Molecular Imaging of Pancreatic Cancer with Antibodies

Molecular Imaging of Pancreatic Cancer with Antibodies

Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma

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Application of 99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma

Abstract: Because the half-life of (99m)Tc is short (6 hr), chA7Fab, which accumulates rapidly in tumors, may be a better carrier of (99m)Tc than intact Mab A7.

Cited by 4 publications

References 26 publications

Molecular Imaging of Pancreatic Cancer with Antibodies

Molecular Imaging of Pancreatic Cancer with Antibodies

Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma

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Application of ^99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma