Preliminary Study on Radioimmunodiagnosis of Experimental Tumor Models Using Technetium-99m-Labeled Anti-C-erbB-2 Monoclonal Antibody

2002 ◽  
Vol 88 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Ananthanarayanan Meenakshi ◽  
Rayala Suresh Kumar ◽  
Venkatraman Ganesh ◽  
Nallathambi Siva Kumar
Keyword(s):  
Monoclonal Antibody ◽  
Early Stage ◽  
Survival Rates ◽  
Premalignant Lesions ◽  
Breast Carcinoma Cell Line ◽  
Tumor Models ◽  
Primary Tumors ◽  
Biodistribution Studies ◽  
Preliminary Study

Aims and background One of the great challenges of oncology is to improve methods for early tumor detection. Diagnosis of premalignant lesions and early stage primary tumors is crucial for the success of cancer therapy and increased survival rates. Growth factor receptors localized to the cell membrane play a vital role in cancer. Monoclonal antibodies labeled with radioisotopes have been used extensively for radioimmunodiagnosis and radioimmunotherapy of various malignancies. A preliminary study on immunoscintigraphy was carried out on animal tumor models using 99mTc-labeled monoclonal antibody CIBCgp185 generated against the C-erbB-2 oncoprotein with a view to develop technologies for in vivo radioimmunodetection and localization of human breast cancer. Methods Mammary tumor xenografts induced using BT474 cells, a breast carcinoma cell line showing overexpression of C-erbB-2, were used for immunoscintigraphic studies. Results Scintigrams showed high radiolabel uptake by the tumor tissue of the mice belonging to the experimental group, whereas in control animals no radiolabel uptake was visualized. Biodistribution studies correlated well with scintiscans. Conclusions The results indicate the potential application of this monoclonal antibody for in vivo diagnosis of occult malignancies of tumors with overexpression of C-erbB-2.

scholarly journals Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts

2021 ◽  
Author(s):  
Kongzhen Hu ◽  
Junqi Li ◽  
Lijuan Wang ◽  
Yong Huang ◽  
Li Li ◽  
...  
Keyword(s):  
Nasopharyngeal Cancer ◽  
High Specificity ◽  
Whole Body ◽  
Cancer Associated Fibroblasts ◽  
Primary Tumors ◽  
Preclinical Evaluation ◽  
Biodistribution Studies ◽  
Pet Ct

Abstract Background The recent development of many different types of radiotracers that target the fibroblast activation protein (FAP) has been promising for tumor diagnosis. Here, we set out to develop 18F-labeled FAP tracers for cancer-associated fibroblast imaging and evaluated the potential of these tracers for clinical application. Methods The non-radioactive reference compounds and labeling precursors were synthesized using organic chemistry and the binding affinities were identified using surface plasmon resonance. Both radioligands (18F-P-FAPI and 18F-FAPI-42) were produced in an automated manner via complexation of Al18F. For in vitro characterization of 18F-P-FAPI and 18F-FAPI-42, we conducted studies to determine the partition coefficients, stability, cellular uptake, internalization, and efflux. In vivo biodistribution studies and microPET imaging of 18F-P-FAPI and 18F-FAPI-42, in comparison to 68Ga-FAPI-04, were conducted on the A549-FAP tumor bearing mice. Finally, one nasopharyngeal cancer patient underwent whole-body PET/CT after being injected with 18F-P-FAPI. Results Both 18F-P-FAPI and 18F-FAPI-42 were successful prepared with high specificity, rapid internalization, and potent affinity binding toward FAP. Compared to 18F-FAPI-42, 18F-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Furthermore, in vivo studies of 18F-P-FAPI in the A549-FAP tumor model indicated a higher tumor uptake than 18F-FAPI-42 and 68Ga-FAPI-04. An initial diagnostic application in patient with nasopharyngeal cancer, 18F-P-FAPI and 18F-FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. Conclusion The radiofluorinated FAP-ligands demonstrated promising characteristics in their preclinical evaluation, and the feasibility of cancer-associated fibroblasts imaging was demonstrated using PET studies.

scholarly journals P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Luisa Palacios-Acedo ◽  
Soraya Mezouar ◽  
Diane Mège ◽  
Lydie Crescence ◽  
Christophe Dubois ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Survival Rates ◽  
Cancer Growth ◽  
Primary Tumors ◽  
Trousseau’S Syndrome ◽  
Pancreatic Cancers ◽  
Cancer Associated Thrombosis

Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau’s syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau’s syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.

A Therapeutic TCR Mimic Monoclonal Antibody for Intracellular PRAME Protein in Leukemias

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2527-2527 ◽  
Author(s):  
Aaron Chang ◽  
Tao Dao ◽  
Andrew Scott ◽  
Leonid Dubrovsky ◽  
Cheng Liu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Retinoic Acid ◽  
Conflicts Of Interest ◽  
Specific Binding ◽  
Retinoic Acid Receptor ◽  
Pharmacokinetic Studies ◽  
Breast Cancers ◽  
Biodistribution Studies

Abstract Preferentially expressed antigen in melanoma (PRAME) is a well-validated target for T cell-based immunotherapy in leukemias and solid tumors. PRAME is a retinoic acid receptor binding protein that prevents retinoic acid-mediated differentiation, proliferation arrest, and apoptosis. As a cancer-testis antigen, PRAME has limited expression in healthy adult tissue that is restricted to the testes, ovaries, and endometrium. However, PRAME is over-expressed in multiple cancers including ALL, AML, melanomas, and breast cancers, making it a specific and highly attractive therapeutic target. PRAME is an intracellular protein making it impossible to target using traditional antibodies and it is not currently druggable. After proteasomal processing, the PRAME300-309 peptide is presented on the cell surface in the context of HLA*A02:01 molecules, for recognition by CD8 T cells. We therefore hypothesized that a TCR-mimic (TCRm) monoclonal antibody that recognizes surface PRAME300-309 presented by HLA*A02:01 could have therapeutic activity. Here, we describe Pr20, a therapeutic TCRm antibody, specific for the PRAME300-309 peptide in complex with HLA*A02:01, identified through a human scFv phage display library screen. Pr20 was engineered into full length human IgG1. Pr20 exhibited specific binding to PRAME300-309 -pulsed TAP-deficient T2 cells and bound PRAME+/ HLA*A02:01+ Ph+ ALL and AML, demonstrating that endogenously presented PRAME300-309 could be recognized by Pr20. Pr20 was determined to have 4 nM binding affinity by scatchard plot analysis. The specific epitope was mapped using alanine substitutions of non-anchor residues in the PRAME300-309 peptide and determined to primarily require the C-terminal residues. Pr20M, an afucosylated form of the antibody with enhanced Fc binding, mediated antibody-dependent cellular cytotoxicity (ADCC) in-vitro in a PRAME+/ HLA*A02:01+ restricted manner. Pharmacokinetic studies in C57BL/6 mice indicated that Pr20M was stable in-vivo and biodistribution studies in HLA*A02:01 transgenic mice suggested that there was no significant antibody sink. Pr20M was therapeutically active in established xenograft leukemia models in NSG mice (T, B, and NK-deficient). Interestingly, Pr20 binding to PRAME+/HLA*A02:01+ melanomas was minimally detectable, but was dramatically increased upon treatment with IFNγ, which also led to an increased sensitivity to ADCC. The data provide rationale for developing TCRm antibodies against intracellular oncoproteins as therapeutics. Disclosures No relevant conflicts of interest to declare.

scholarly journals 64cu-DOTA-Anti-CD33 PET-CT Imaging for Acute Myeloid Leukemia and Image-Guided Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2747-2747 ◽  
Author(s):  
Srideshikan Sargur Madabushi ◽  
Darren Zuro ◽  
Jamison Brooks ◽  
Bijender Kumar ◽  
Liliana E Parra ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Plan ◽  
Ct Imaging ◽  
Whole Body ◽  
Non Invasive ◽  
Image Guided ◽  
Biodistribution Studies ◽  
Pet Ct ◽  
Total Marrow Irradiation

Abstract Introduction: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results a poor survival outcome. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). Although non-invasive positron emission tomography (PET) imaging has been developed for almost all solid tumors and some hematological malignancies, there is currently no non-invasive imaging specific to AML available, representing an unmet clinical need. About 85% of AML cells express CD33, and expression levels of CD33 has been correlated with poor survival outcomes (Pollard et al., Blood (2012)), making it an ideal candidate for immuno-PET. Therefore, our primary goal is to develop anti-CD33 immuno-PET for detecting CD33+ AML. The secondary goal is to assess the feasibility of CD33 PET image-guided external beam targeted radiation delivery in combination with chemotherapy (AraC). Methods: Murine anti-human CD33 monoclonal antibody clone p67.6 was conjugated to DOTA and radiolabeled with Cu-64 for imaging studies. In vivo PET-CT imaging and bio distribution of 64Cu-DOTA-anti-CD33 in vivo was carried out in NSG mice bearing CD33+ (MV4-11, HL60) AML cells. CD33-negative MM1s cells (multiple myeloma) were used as negative control. The AML and MM bearing mice were injected with 64Cu-DOTA-anti-CD33 (100 µCi/10 µg) and serial PET imaged at 24-48 h. We developed a functional total marrow irradiation (fTMI) treatment, where mice received total marrow irradiation (TMI) (2 Gy) and boost radiation (2 Gy) to regions with increased CD33 activity, followed by 2 days of AraC (40 mg/kg) and 24h later a bone marrow transplant. Furthermore, a humanized anti-human CD33 monoclonal antibody was generated and tested for immunogenicity against CD33 in AML cell lines and patient samples for future clinical studies. Results: PET-CT imaging and biodistribution studies of 64Cu-DOTA-anti-CD33 clearly indicates a CD33+ PET signal in the femur, tibia, humerus joints, L spine and spleen in AML-bearing mice, but not in multiple myeloma-bearing mice or in cold anti-CD33-DOTA treated leukemic mice (Figure 1A and B). Our new imaging method was able to detect CD33+ AML with a favorable sensitivity (71.4%) and specificity (100%). Based on detailed whole-body 3D imaging and validated with biodistribution studies, we discovered preferential regions in the skeletal system with differential CD33 activity, indicating the spatial heterogeneity of AML. CD33+ PET intensity was observed in the following descending order: femur≥lspine>humerus>tibia (Figure 1C). Next, using the PET-CT images, we targeted these CD33-active regions using the fTMI treatment plan. We have developed a unique irradiation system which allows targeting only skeletal tissues while sparing major organs like gut, lung and liver, unlike conventional total body irradiation (TBI). This approach will also provide an opportunity to escalate doses to specific regions in the body without damaging other unintended targets. The fTMI (2 Gy TMI and 2 Gy boost) treatment plan increased the medial survival of the mice to 43 days versus that of untreated control mice (26 days) or AraC treated mice (33 days) Figure(1D). Since the preclinical study was carried out using murine anti-CD33 antibody clone p67.6, we further tested the newly generated humanized anti-human-CD33 monoclonal antibody. This humanized antibody detects CD33 in both AML cell lines and human patient sample (Fig 1E). Conclusion: This study is the first to use an anti-CD33 monoclonal antibody for non-invasive immuno-PET-based imaging for AML detection, showing high sensitivity and specificity. This whole body imaging may be useful for AML diagnosis not only in the entire skeletal system, but also in the extramedullary organs, and for longitudinal monitoring of treatment response. Unlike conventional TBI, Image-guided fTMI along with conventional chemotherapy may result in an improved prognosis, as unintended major organs are spared from radiation. Disclosures Vallera: GT Biopharma: Consultancy, Research Funding. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau.

Optimal Saturated Neuropilin-1 Expression in Normal Tissue Maximizes Tumor Exposure to Anti-Neuropilin-1 Monoclonal Antibody

2020 ◽  
Vol 19 (18) ◽  
pp. 2269-2275 ◽  
Author(s):  
Chao Ma ◽  
Xiaofeng Dou ◽  
Jianghua Yan ◽  
Shengyu Wang ◽  
Rongshui Yang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Normal Tissue ◽  
Optimal Dose ◽  
Tumor Xenograft ◽  
Dependent Manner ◽  
Tumor Uptake ◽  
Biodistribution Studies ◽  
Neuropilin 1 ◽  
Unlabeled Antibody

Background: As involved in tumor angiogenesis, Neuropilin Receptor type-1 (NRP-1) serves as an attractive target for cancer molecular imaging and therapy. Widespread expression of NRP-1 in normal tissues may affect anti-NRP-1 antibody tumor uptake. Objective: To assess a novel anti-NRP-1 monoclonal antibody A6-11-26 biodistribution in NRP-1 positive tumor xenograft models to understand the relationships between dose, normal tissue uptake and tumor uptake. Methods: The A6-11-26 was radiolabeled with 131I and the mice bearing U87MG xenografts were then administered with 131I-labelled A6-11-26 along with 0, 2.5, 5, and 10mg·kg-1 unlabelled antibody A6-11-26. Biodistribution and SPECT/CT imaging were evaluated. Results: 131I-A6-11-26 was synthesized successfully by hybridoma within 60min. It showed that most of 131IA6- 11-26 were in the plasma and serum (98.5 ± 0.16 and 88.9 ± 5.84, respectively), whereas, less in blood cells. For in vivo biodistribution studies, after only injection of 131I-A6-11-26, high levels of radioactivity were observed in the liver, moderate level in lungs. However, liver and lungs radioactivity uptakes could be competitively blocked by an increasing amount of unlabeled antibody A6-11-26, which can increase tumor radioactivity levels, but not in a dose-dependent manner. A dose between 10 and 20mg·kg-1 of unlabeled antibody A6-11-26 may be the optimal dose that maximized tumor exposure. Conclusion: Widespread expression of NRP-1 in normal tissue may affect the distribution of A6-11-26 to tumor tissue. An appropriate antibody A6-11-26 dose would be required to saturate normal tissue antigenic sinks to achieve acceptable tumor exposure.

scholarly journals Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma

2018 ◽  
Vol 10 (467) ◽  
pp. eaat5933 ◽  
Author(s):  
Claudio R. Scafoglio ◽  
Brendon Villegas ◽  
Gihad Abdelhady ◽  
Sean T. Bailey ◽  
Jie Liu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Glucose Transporter ◽  
Early Stage ◽  
Premalignant Lesions ◽  
Low Grade ◽  
Lung Tumorigenesis ◽  
Glucose Transporter 2 ◽  
Potential Marker

The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.

scholarly journals LKB1 inactivation modulates chromatin accessibility to drive metastatic progression

2021 ◽  
Author(s):  
Sarah Elisabeth Pierce ◽  
Jeffrey M Granja ◽  
M Ryan Corces ◽  
Jennifer J Brady ◽  
Min K Tsai ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Early Stage ◽  
Suppressor Gene ◽  
Chromatin Accessibility ◽  
Driver Mutations ◽  
In Vivo Model ◽  
Metastatic Progression ◽  
Primary Tumors

Metastasis is the leading cause of cancer-related deaths, enabling cancer cells to expand to secondary sites and compromise organ function. Given that primary tumors and metastases often share the same constellation of driver mutations, the mechanisms driving their distinct phenotypes are unclear. Here, we show that inactivation of the frequently mutated tumor suppressor gene, liver kinase B1 (LKB1), has evolving effects throughout lung cancer progression, leading to the differential epigenetic re-programming of early-stage primary tumors compared to late-stage metastases. By integrating genome-scale CRISPR/Cas9 screening with bulk and single-cell multi-omic analyses, we unexpectedly identify LKB1 as a master regulator of chromatin accessibility in lung adenocarcinoma primary tumors. Using an in vivo model of metastatic progression, we further reveal that loss of LKB1 activates the early endoderm transcription factor SOX17 in metastases and a metastatic-like sub-population of cancer cells within primary tumors. SOX17 expression is necessary and sufficient to drive a second wave of epigenetic changes in LKB1-deficient cells that enhances metastatic ability. Overall, our study demonstrates how the downstream effects of an individual driver mutation can appear to change throughout cancer development, with implications for stage-specific therapeutic resistance mechanisms and the gene regulatory underpinnings of metastatic evolution.

scholarly journals Inhibitory Effects of Doxycycline on Tumor Progression In vitro and on Metastases in Early-Stage Osteosarcoma Xenografts Mice.

2022 ◽  
Author(s):  
Argyris Costas Hadjimichael ◽  
Athanasios F. Foukas ◽  
Evangelia Papadimitriou ◽  
Chrysostomi Peristiani ◽  
Ioannis Chaniotakis ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Early Stage ◽  
Vascular Endothelial ◽  
Primary Tumors ◽  
Protein Levels ◽  
High Propensity ◽  
And Migration ◽  
Endothelial Growth Factor

Abstract Introduction. Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis, effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cells’ growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo. Methods. In vitro, the effect of Dox was measured in MG-63 and 143B human OS cells’ viability, apoptosis, and migration. In vivo, highly metastatic143B cells were orthotopically implanted into the tibia of SCID mice and tumor growth as well as pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined. Results. Dox decreased the viability, inhibited the migration, and induced the apoptosis of OS cells in vitro. In vivo, Dox significantly enhanced tumor necrosis at primary OS sites, similarly to its in vitro effect. It also decreased the expression of Ki67, metalloproteinases 2 and 9 (MMP2 and MMP9), vascular endothelial growth factor A (VEGFA) and Ezrin in primary tumors. It also decreased the circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice in both non-amputated and early amputated xenografts. Conclusions. Our results suggest that adjuvant administration of Dox may decrease OS growth and development of pulmonary metastases. Administration of Dox in combination with surgical resection and standard chemotherapeutic protocols in the early-stages of OS treatment is also supported. Moreover, Dox administration prior to the development of clinically detectable pulmonary macrometastases, is associated with enhanced clinically benefits from its anti-metastatic effect.

scholarly journals Mouse-Derived Isograft (MDI) In Vivo Tumor Models I. Spontaneous sMDI Models: Characterization and Cancer Therapeutic Approaches

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 244 ◽  
Author(s):  
Peter Jantscheff ◽  
Janette Beshay ◽  
Thomas Lemarchand ◽  
Cynthia Obodozie ◽  
Christoph Schächtele ◽  
...  
Keyword(s):  
Immune Cell ◽  
High Sensitivity ◽  
Mouse Strains ◽  
In Vivo Model ◽  
Tumor Models ◽  
Primary Tumors ◽  
Passage Number ◽  
Low Passage ◽  
Long Term Observation

Syngeneic in vivo tumor models are valuable for the development and investigation of immune-modulating anti-cancer drugs. In the present study, we established a novel syngeneic in vivo model type named mouse-derived isografts (MDIs). Spontaneous MDIs (sMDIs) were obtained during a long-term observation period (more than one to two years) of naïve and untreated animals of various mouse strains (C3H/HeJ, CBA/J, DBA/2N, BALB/c, and C57BL/6N). Primary tumors or suspicious tissues were assessed macroscopically and re-transplanted in a PDX-like manner as small tumor pieces into sex-matched syngeneic animals. Nine outgrowing primary tumors were histologically characterized either as adenocarcinomas, histiocytic carcinomas, or lymphomas. Growth of the tumor pieces after re-transplantation displayed model heterogeneity. The adenocarcinoma sMDI model JA-0009 was further characterized by flow cytometry, RNA-sequencing, and efficacy studies. M2 macrophages were found to be the main tumor infiltrating leukocyte population, whereas only a few T cells were observed. JA-0009 showed limited sensitivity when treated with antibodies against inhibitory checkpoint molecules (anti-mPD-1 and anti-mCTLA-4), but high sensitivity to gemcitabine treatment. The generated sMDI are spontaneously occurring tumors of low passage number, propagated as tissue pieces in mice without any tissue culturing, and thus conserving the original tumor characteristics and intratumoral immune cell populations.

scholarly journals Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ping Zhao ◽  
Xiaoyang Yang ◽  
Shibo Qi ◽  
Hongguang Liu ◽  
Han Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Stage ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Dismal Prognosis ◽  
Epidermal Growth

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCCin vivo.

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