Optical Imaging of Renal Cell Carcinoma with Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab

Muselaers, Stijn; Stillebroer, Alexander B.; Rijpkema, Mark; Franssen, Gerben M.; Oosterwijk, Egbert; Mulders, Peter F.A.; Oyen, Wim J.G.; Boerman, Otto C.

doi:10.2967/jnumed.114.137356

Cited by 24 publications

(17 citation statements)

References 26 publications

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“…5E). In a clinical setting, an optical imaging agent based on Bs-F(ab) 2 would be of utility to locate the tumor and guide the removal of the tumor foci and surgical margins (42). Similar approaches have shown success in the clinic for the detection/resection of lymph nodes and in patients with ovarian cancer (43, 44).…”

Section: Discussionmentioning

confidence: 99%

Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry

Luo

Hernandez

Hong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Early diagnosis remains a task of upmost importance for reducing cancer morbidity and mortality. Successful development of highly specific companion diagnostics targeting aberrant molecular pathways of cancer is needed for sensitive detection, accurate diagnosis, and opportune therapeutic intervention. Herein, we generated a bispecific immunoconjugate [denoted as Bs-F(ab) Cu-NOTA-Bs-F(ab) 2 was able to visualize small U87MG tumor nodules (<5 mm in diameter), owing to high tumor uptake (31.4 ± 10.8%ID/g at 36 h postinjection) and a tumor/muscle ratio of 76.4 ± 52.3, which provided excellent sensitivity for early detection. Finally, we successfully confirmed the feasibility of a ZW800-1-labeled Bs-F(ab) 2 for nearinfrared fluorescence imaging and image-guided surgical resection of U87MG tumors. More importantly, our rationale can be used in the construction of other disease-targeting bispecific antibody fragments for early detection and diagnosis of small malignant lesions.

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Section: Discussionmentioning

confidence: 99%

Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry

Luo

Hernandez

Hong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The cell line was previously described by Ebert et al 9 and tested for authenticity by short tandem repeat profiling in August 2013 (DSMZ, Braunschweig, Germany). As we recently described our results with dual-labeled girentuximab in multiple tumor cell lines, no additional studies with a CAIX-negative control tumor group were performed in this study 7 .…”

Section: Cell Lines and Induction Of Tumorsmentioning

confidence: 95%

“…Because of the high and specific targeting of G250 in all CAIX-positive lesions (both primary tumors and metastases), this antibody could act as a potent carrier for the delivery of both the radiotracer and the NIR dye in these lesions. As we recently described, such a dual modality imaging system enables preoperative Single Photon Emission Computed Tomography (SPECT) and intraoperative tumor detection by means of the radioactive and NIR signal 7 . In this study, we describe 111 Indium ( 111 In)-DTPA-G250-IRDye800CW and show the feasibility of dual modality imaging and image-guided surgery in an intraperitoneal (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250

et al. 2015

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“…Indeed, CA IX is almost homogeneously over-expressed in the ccRCC subtype [18–23,25,26]. Given the favorable tissue distribution, the potential of CA IX targeting of RCC for diagnosis or therapy has also been studied [27,28]. Due to the unique molecular attribute of RCC, CA IX is regarded as an excellent target for diagnosis and possibly for targeted therapy [20– 22,25,29].…”

Section: Introductionmentioning

confidence: 99%

Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages

Alsaab

Alzhrani

et al. 2018

Biomaterials

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Drug resistance is one of the significant clinical burden in renal cell carcinoma (RCC). The development of drug resistance is attributed to many factors, including impairment of apoptosis, elevation of carbonic anhydrase IX (CA IX, a marker of tumor hypoxia), and infiltration of tumorigenic immune cells. To alleviate the drug resistance, we have used Sorafenib (Sor) in combination with tumor hypoxia directed nanoparticle (NP) loaded with a new class of apoptosis inducer, CFM 4.16 (C4.16), namely CA IX-C4.16. The NP is designed to selectively deliver the payload to the hypoxic tumor (core), provoke superior cell death in parental (WT) and Everolimus-resistant (Evr-res) RCC and selectively downmodulate tumorigenic M2-macrophage. Copper-free 'click' chemistry was utilized for conjugating SMA-TPGS with Acetazolamide (ATZ, a CA IX-specific targeting ligand). The NP was further tagged with a clinically approved NIR dye (S0456) for evaluating hypoxic tumor core penetration and organ distribution. Imaging of tumor spheroid treated with NIR dye-labeled CA IX-SMA-TPGS revealed remarkable tumor core penetration that was modulated by CA IX-mediated targeting in hypoxic-A498 RCC cells. The significant cell killing effect with synergistic combination index (CI) of CA IX-C4.16 and Sor treatment suggests efficient reversal of Evr-resistance in A498 cells. The CA IX directed nanoplatform in combination with Sor has shown multiple benefits in overcoming drug resistance through (i) inhibition of p-AKT, (ii) upregulation of tumoricidal M1 macrophages resulting in induction of caspase 3/7 mediated apoptosis of Evr-res A498 cells in macrophage-RCC co-culturing condition, (iii) significant in vitro and in vivo Evr-res A498 tumor growth inhibition as compared to individual therapy, and (iv) untraceable liver and kidney toxicity in mice. Near-infrared (NIR) imaging of CA IX-SMA-TPGS-S0456 in Evr-res A498 RCC model exhibited significant accumulation of CA IX-oligomer in tumor core with >3-fold higher tumor uptake as compared to control. In conclusion, this proof-of-concept study demonstrates versatile tumor hypoxia directed nanoplatform that can work in synergy with existing drugs for reversing drug-resistance in RCC accompanied with re-education of tumor-associated macrophages, that could be applied universally for several hypoxic tumors.

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Optical Imaging of Renal Cell Carcinoma with Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab

Cited by 24 publications

References 26 publications

Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry

Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250

Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages

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