ImmunoPET imaging of tissue factor expression in pancreatic cancer with 89Zr-Df-ALT-836

Hernandez, Reinier; England, Christopher G.; Yang, Yunan; Valdovinos, Hector F.; Liu, Bai; Wong, Hing C.; Barnhart, Todd E.; Cai, Weibo

doi:10.1016/j.jconrel.2017.08.029

Cited by 19 publications

(20 citation statements)

References 31 publications

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“…Yet, with the “bone-seeking” nature of 89 Zr making these localizations preferential sites for bone accumulation too, this could directly impact immuno-PET imaging and its use as a therapeutic planning companion. Indeed, multiple preclinical studies reported the use of 89 Zr-labeled mAbs with elevated uptakes in the bones which (although not always described) clearly altered PET images’ interpretations [22,23,24,28,29]. These results are also in agreement with precedent findings of the use of immuno-PET as a scouting procedure before radioimmunotherapy (RIT) with large disparity of the distribution of 89 Zr-conjugates and RIT conjugates [30,31,32].…”

Section: Discussionmentioning

confidence: 99%

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Bailly

Gouard

Guérard

et al. 2019

IJMS

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Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

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Section: Discussionmentioning

confidence: 99%

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Bailly

Gouard

Guérard

et al. 2019

IJMS

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“…This phenomenon may ensure the effect of PIT by additional exposure of NIR 24 h later. Our present study is the first ever report of NIR-PIT targeting TF with 1849-ICG, although there have been studies regarding the targeting of TF for diagnostic imaging[14-16] or radioisotope therapy[17]. Since TF is expressed not only on tumor cell surface, but also, in tumor stroma[37] and on tumor-associated vascular endothelial cells[38], our NIR-PIT with 1849-ICG may possibly target all of them.…”

Section: Discussionmentioning

confidence: 99%

“…We reported the development of Alexa Flour-647-labeled anti-TF antibody 1849 probe for fluorescence imaging in a TF-overexpressing human pancreatic cancer xenograft model[11] and an 111 In-labeled anti-TF antibody 1849 probe for immuno- single-photon emission computed tomography (SPECT) imaging in glioma model[13] and pancreatic cancer models (manuscript under preparation). Cai et al[14,15] have successfully developed a radiotracer for immuno-PET (positron emission computed tomography) imaging of in vivo TF expression in pancreatic cancer and breast cancer models[16]. Wang et al[17] labeled anti-TF antibody with 90 Y and reported its radiotherapeutic effect on human xenograft NSCLC tumors in nude mice.…”

Section: Introductionmentioning

confidence: 99%

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

Aung¹,

Tsuji²,

Sugyo³

et al. 2018

WJG

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AIMTo investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor (TF) antibody conjugated to indocyanine green (ICG) in a pancreatic cancer model.METHODSNear-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2b anti-TF monoclonal antibody 1849 (anti-TF 1849) to a NIR photosensitizer, ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PIT-induced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIR-PIT, tumor-bearing mice were separated into 5 groups: (1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure (50 J/cm2) on two consecutive days (Days 1 and 2); (2) NIR light exposure (50 J/cm2) only on two consecutive days (Days 1 and 2); (3) 100 μg of 1849-ICG i.v. administration; (4) 100 μg of unlabeled anti-TF 1849 i.v. administration; and (5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical (IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments.RESULTSHigh TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38 (NIR-PIT) vs 5.42 ± 1.61 (Untreated), vs 4.90 ± 0.87 (NIR), vs 4.28 ± 1.87 (1849-ICG), vs 4.35 ± 1.42 (anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells (a cell proliferation marker) by IHC examination.CONCLUSIONThe TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.

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“…Low/moderate expression is seen in pancreatitis, whereas normal pancreatic parenchyma does only minimally express TF [ 127 ]. Further evaluation with the available TF-targeted small molecule inhibitors is warranted to address the potential for early detection and monitoring of PDAC [ 130 , 131 , 132 ].…”

Section: Molecular Targets In Pancreatic Ductal Adenocarcinoma (Pdac)mentioning

confidence: 99%

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

Cancers

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Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

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ImmunoPET imaging of tissue factor expression in pancreatic cancer with 89Zr-Df-ALT-836

Cited by 19 publications

References 31 publications

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

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