Radioimmunodiagnosis of Human-Derived Squamous Cell Carcinoma

Wahl, Richard L.; Kimmel, Kathryn A.; Beierwaltes, William H.; Carey, Thomas E.

doi:10.1089/hyb.1987.6.111

Cited by 14 publications

(7 citation statements)

References 11 publications

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“…The attenuation values observed for the negative control samples that were targeted with gold nanorods (larynx and oral cancer cells targeted with nanorods that are coated with non matching antibodies, and normal fibroblast and melanoma cells targeted with A9 antibodies) revealed relatively low non-specific binding (58, 54, 50, 62 HU, respectively), and demonstrate that head and neck tumors may show a likely enhancement of 3-4 times the local contrast of non-targeted tissue in vivo . Such a specificity and local enhancement is consistent with a previous study investigating the potential use of UM-A9 as a radiolabeled imaging agent for human squamous carcinoma tumors in vivo 27. The attenuation value observed for the positive control sample, the bare gold nanorods, is 158 HU; this high number was expected since the sample contained a high concentration of gold (2.5 mg/mL).…”

Section: Ct Scanssupporting

confidence: 90%

“…Previously it has been demonstrated that SCC is characterized by significant over-expression of the A9 antigen 24, which is also called the alpha6beta4 integrin 25, and that there is a strong correlation between the A9 expression level and metastatic behavior 26. It has also been demonstrated that the UM-A9 antibody can home onto SCC tumors in vivo 27. An additional reason for choosing head and neck cancer was because one of its major diagnostic challenges today is a reliable detection of involved lymph nodes, since their status is one of the most important prognosis predictors, and is also critical for appropriate treatment.…”

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confidence: 99%

“…26 It has also been demonstrated that the UM-A9 antibody can home onto SCC tumors in vivo. 27 An additional reason for choosing head and neck cancer was because one of its major diagnostic challenges today is a reliable detection of involved lymph nodes because their status is one of the most important prognosis predictors and is also critical for appropriate treatment. However, assessment of lymph nodes based on structural imaging features is limited in sensitivity and specificity and fails to distinguish between non-neoplastic and malignant processes.…”

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confidence: 99%

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Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer

et al. 2008

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X-ray based computed tomography (CT), is among the most convenient imaging/diagnostic tools in hospitals today in terms of availability, efficiency and cost. However, in contrast to magnetic resonance imaging (MRI) and various nuclear medicine imaging modalities, CT is not considered a molecular imaging modality since targeted and molecularly specific contrast agents have not yet been developed. Here we describe a targeted molecular imaging platform that enables, for the first time, cancer detection at the cellular and molecular level with standard clinical CT. The method is based on gold nano-probes that selectively and sensitively target tumor selective antigens, while inducing distinct contrast in CT imaging (increased x-ray attenuation). We present an in vitro proof of principle demonstration for head and neck cancer, showing that the attenuation coefficient for the molecularly targeted cells is over 5 times higher than for identical but untargeted cancer cells or for normal cells. We expect this novel imaging tool to lead to significant improvements in cancer therapy, due to earlier detection, accurate staging and micro-tumor identification.Imaging plays a critical role in overall cancer management; in diagnostics, staging, radiation planning and evaluation of treatment efficiency. Standard clinical imaging modalities such as CT, MRI and ultrasound, can be categorized as structural imaging modalities; they are able to identify anatomical patterns and to provide basic information regarding tumor location, size and spread based on endogenous contrast. However, these imaging modalities are not efficient in detecting tumors and metastases that are smaller than 0.5 cm, and they can barely distinguish between benign and cancerous tumors 1 .Molecular imaging is an emerging field that integrates molecular biology with in vivo imaging, in order to gain information regarding biological processes and to identify diseases based on molecular markers, which usually appear before the clinical presentation of the disease. Currently, positron emission tomography and single photon emission tomography are the main molecular imaging modalities in clinical use, however, they provide only functional information regarding molecular processes and metabolites, which is indirect and nonspecific to distinct cells or diseases 2,3 . Recently, various types of targeted nano-probes have been developed for optical and MRI molecular imaging, such as superparamagnetic nanoparticles 4-7 ; quantum dots [8][9][10] and gold nanoparticles as cancer optical imaging probes [11][12][13] .

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Section: Ct Scanssupporting

confidence: 90%

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confidence: 99%

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confidence: 99%

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Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer

et al. 2008

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“…Whereas extensive studies using radiolabelled MAbs have been performed for ovarian or colorectal carcinomas (Colcher et al, 1988;Epenetos et al, 1986) there is only limited experience in the use of MAbs for detection of SCCs. Wahl et al (1987) used the A9 antibody with moderate success to image SCC xenografts, obtaining tumor to blood ratios of 1.84 at day 7 after i.v. injection.…”

Section: Discussionmentioning

confidence: 99%

Localization and imaging of radiolabelled monoclonal antibody against squamous‐cell carcinoma of the head and neck in tumor‐bearing nude mice

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Balm

Brakkee

et al. 1989

Intl Journal of Cancer

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Nude mice carrying human squamous-cell carcinoma xenografts were given i.v. injections of radiolabelled monoclonal antibodies (MAbs). MAb E 48, which reacts with squamous-cell carcinomas, was labelled with 131I, while a second control MAb of similar immunoglobulin subclass was labelled with 125I. Both antibodies were injected simultaneously, then the mice were scanned with a gamma camera or their tissues were removed and antibody uptake was calculated as a percentage of the injected dose. Uptake of E 48 reached a peak value of 16%/g on day 3, while uptake of the control antibody was less than 1.8%/g. By 24 hr after injection tumor could be visualized without subtraction techniques. At days 3 and 7, only xenografts were visible on imaging. These findings suggest that E 48 is capable of high specificity in targeting isotopes to squamous-cell carcinomas in an experimental setting.

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“…Antibodies possibly suitable for radioimmunoimaging of head and neck squamous cell carcinoma exist already (12)(13)(14). Radioimmunodetection based on antibodies to retroviral-PI SE-related material might also be applicable to head and neck carcinomas, as these produce low molecular weight factors ( c 25 kDa), capable of inhibiting the chemotaxis of mononuclear phagocytes (27), the effect of which can be neutralized by antibodies to P15E.…”

Section: Discussionmentioning

confidence: 99%