Biodistribution of iodine-125 labeled monoclonal antibody/Interleukin-2 immunoconjugate in athymic mice bearing human tumor xenografts

Nakamura, Kayoko; Kubo, Atsushi

doi:10.1002/(sici)1097-0142(19971215)80:12+<2650::aid-cncr41>3.0.co;2-8

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…With chTNT-3/IL-2 and chemotherapy pretreatment, we show no increase in 125 I-chTNT-3 uptake in IL-2-sensitive normal tissues such as, lung, liver, and kidneys. In agreement with our results using chTNT-3/IL-2, IL-2 conjugated to an anti-CEA antibody resulted in enhanced vascular permeability in CEA + tumor but not host organs (43). The use of chTNT-3 as opposed to an antibody to a single antigen on specific tumors offers several benefits.…”

Section: Discussionsupporting

confidence: 91%

“…IL-2 is known to enhance vascular permeability, as exemplified by its induction of vascular leak syndrome (41). Other studies have also demonstrated the effects of IL-2 on vascular permeability in tumor models (15, 16, 18, 42, 43). Pretreatment with free IL-2 increased tumor uptake of radiolabeled antibodies, but also increased uptake in normal lung, liver, spleen, and kidney in a mouse xenograft model (42).…”

Section: Discussionmentioning

confidence: 92%

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Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models

Jang

Khawli

Park

et al. 2013

Molecular Cancer Therapeutics

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Current strategies in cancer treatment employ combinations of different treatment modalities, which include chemotherapy, radiotherapy, immunotherapy, and surgery. Consistent with that approach, the present study demonstrates how chemotherapeutic agents can potentiate the delivery of radiolabeled, necrosis-targeting antibodies (chTNT-3, NHS76) to tumor. All chemotherapeutics in this study (5-fluorouracil, etoposide, vinblastine, paclitaxel, and doxorubicin) resulted in statistically significant increases in tumor uptake of radiolabeled antibodies and their F(ab')2 fragments compared to no pretreatment with chemotherapy. Labeled antibodies were administered at various time points following a single dose of chemotherapy in multiple tumor models, and the biodistribution of the antibodies were determined by measuring radioactivity in harvested tissues. MicroPET/CT was also done to demonstrate clinical relevancy of using chemotherapy pretreatment to increase antibody uptake. Results of biodistribution and imaging data reveal specific time frames following chemotherapy when necrosis-targeting antibodies are best delivered, either for imaging or radiotherapy. Thus, the present work offers the prospect of using cytoreductive chemotherapy to increase tumor accumulation of select therapeutic antibodies, especially when combined with other forms of immunotherapy, for the successful treatment of solid tumors.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 92%

Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models

Jang

Khawli

Park

et al. 2013

Molecular Cancer Therapeutics

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“…For example, small-size proteins and antibody fragments are cleared via the renal route, whereas larger-size antibodies are removed via the hepatobiliary route [140]. Further, nontargeted uptake of antibodies can occur differently based on the radioactive element bound to the antibody [141, 142]. The catabolized fragments of radiolabeled antibodies have been shown to pose a radiation risk to renal organs [143].…”

Section: Mpi For Cell Tracking and Immunotherapymentioning

confidence: 99%

Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis

et al. 2023

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Magnetic particle imaging (MPI) is a new tracer-based imaging modality that is useful in diagnosing various pathophysiology related to the vascular system and for sensitive tracking of cytotherapies. MPI uses nonradioactive and easily assimilated nanometer-sized iron oxide particles as tracers. MPI images the nonlinear Langevin behavior of the iron oxide particles and has allowed for the sensitive detection of iron oxide-labeled therapeutic cells in the body. This review will provide an overview of MPI technology, the tracer, and its use in vascular imaging and cytotherapies using molecular targets.

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“…Subsequent studies were done by coupling IL-2 to tumor-specific antibodies for localized enhancement of vascular permeability in the tumor. IL-2 -conjugated anti-CEA mAb exhibited a f4-fold increased uptake in tumor compared with unconjugated antibody administered alone or following pretreatment of free IL-2 without affecting the uptake in the nontarget tissues (47). Through a series of studies, Epstein et al have established that the localization of IL-2 in the tumor need not be specific for inducing vascular permeability in the tumor (45, 48 -50).…”

Section: Crossing Endothelium By Altering Vascular Permeabilitymentioning

confidence: 99%

Optimization of Radioimmunotherapy of Solid Tumors: Biological Impediments and Their Modulation

Jain

Venkatraman

Batra

2007

Clinical Cancer Research

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In contrast to the overwhelming success of radiolabeled antibodies in treating hematologic malignancies, only modest success has been achieved in the radioimmunotherapy of solid tumors. One of the major limitations in successful application of radioimmunotherapy is the large molecular size of the intact immunoglobulin that results in prolonged serum half-life and poor tumor penetration and uptake.With the advent of antibody engineering, small molecular weight antibody fragments exhibiting improved pharmacokinetics and tumor penetration have been generated. However, their clinical application has been limited by suboptimal tumor uptake and short tumor residence time. There is a greater realization that optimization of the molecular size of the antibodies alone is not sufficient for clinical success of radioimmunotherapy. In addition to their size, radiolabeled antibodies encounter other impediments before reaching their target antigens expressed on the cell surface of solid tumors. Some of the barriers include poor blood flow in large tumors, permeability of vascular endothelium, elevated interstitial fluid pressure of tumor stroma, and heterogeneous antigen expression. Recent research has considerably improved our understanding and appreciation of these forces, and the new wave of optimization strategies involves the use of biological modifiers to modulate the impediments posed by solid tumors. In combination with radiolabeled antibodies, various agents are being used to improve the tumor blood flow, enhance vascular permeability, lower tumor interstitial fluid pressure by modulating stromal cells and extracellular matrix components, up-regulate the expression of target antigens, and improve the penetration and retention of the radiopharmaceuticals. This review outlines ongoing research efforts involving biological modifiers to optimize the uptake and efficacy of radiolabeled antibodies for the treatment of solid tumors.

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Biodistribution of iodine-125 labeled monoclonal antibody/Interleukin-2 immunoconjugate in athymic mice bearing human tumor xenografts

Abstract: These studies indicate that the administration of radiolabeled MoAb/IL-2 double conjugate may enhance the therapeutic potential of radiolabeled MoAb without any pretreatment with IL-2 or repeated injection of MoAb.

Cited by 6 publications

References 13 publications

Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models

Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models

Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis

Optimization of Radioimmunotherapy of Solid Tumors: Biological Impediments and Their Modulation

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