Intracellular catabolism of radiolabeled anti-CD3 antibodies by leukemic T cells

Geissler, F; Anderson, Susan K.; Press, Oliver W.

doi:10.1016/0008-8749(91)90060-o

Cited by 75 publications

(69 citation statements)

References 32 publications

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“…elimination from the cell and is most probably related to intrinsic physical properties of the linker and metal (Geissler et al, 1991;Duncan and Welch, 1993;Zhu et al, 1997;Perera et al, 2007;Diagaradjane et al, 2008;Boswell et al, 2010 (Yip et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Near Infrared Fluorescent Labeling of Monoclonal Antibodies as a Tool for Tissue Distribution

et al. 2014

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The pharmacokinetic (PK) behavior of monoclonal antibodies (mAbs) is influenced by target-mediated drug disposition, off-target effects, antidrug antibody-mediated clearance, and interaction with fragmentcrystallizable domain (Fc) receptors such as neonatal Fc receptor. All of these interactions hold the potential to impact mAb biodistribution. Near infrared (NIR) fluorescent probes offer an approach complementary to radionuclides to characterize drug disposition. Notably, the use of IRDye800 (IR800; LI-COR, Lincoln, NE) as a protein-labeling agent in preclinical work holds the potential for quantitative tissue analysis. Here, we tested the utility of the IR800 dye as a quantitative mAb tracer during pharmacokinetic analysis in both plasma and tissues using a model mouse monoclonal IgG1 (8C2) labeled with £1.5 molecules of IR800. The plasma PK parameters derived from a mixture of IR800-8C2 and 8C2 dosed intravenously to C57BL/6 mice at 8 mg/kg exhibited a large discrepancy in exposure depending on the method of quantitation [CL plasma = 8.4 ml/d per kilogram (NIR fluorescence detection) versus 2.5 ml/d per kilogram (enzyme-linked immunosorbent assay)]. The disagreement between measurements suggests that the PK of 8C2 is altered by addition of the IR800 dye. Additionally, direct fluorescence analysis of homogenized tissues revealed several large differences in IR800-8C2 tissue uptake when compared with a previously published study using [125 I]8C2, most notably an over 4-fold increase in liver concentration. Finally, the utility of IR800 in combination with whole body imaging was examined by comparison of IR800-8C2 levels observed in animal sagittal cross-sections to those measured in homogenized tissues. Our results represent the first PK analysis in both mouse plasma and tissues of an IR800-mAb conjugate and suggest that mAb disposition is significantly altered by IR800 conjugation to 8C2.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Near Infrared Fluorescent Labeling of Monoclonal Antibodies as a Tool for Tissue Distribution

et al. 2014

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“…It is well known that radiohalogenated peptides compared with radiometal chelated peptides exhibit different metabolic patterns and clearance routes (27)(28)(29)(30). The fast clearance of radiohalogenated peptides from normal tissues is sometimes an advantage for the development of imaging probes.…”

Section: Introductionmentioning

confidence: 99%

“…The significant hepatobiliary accumulation and retention of the 64 Cu-labeled compound is primarily due to the release of uncoordinated 64 Cu from the radio-labeled product by decomposition in the blood or trans-chelation in the liver (26). Further studies to optimize the biodistribution of 64 Cu-DOTA-NAPamide and to achieve better imaging quality are needed.It is well known that radiohalogenated peptides compared with radiometal chelated peptides exhibit different metabolic patterns and clearance routes (27)(28)(29)(30). The fast clearance of radiohalogenated peptides from normal tissues is sometimes an advantage for the development of imaging probes.…”

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confidence: 99%

Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled -Melanocyte-Stimulating Hormone Analog

Cheng¹,

Zhang²,

Graves³

et al. 2007

Journal of Nuclear Medicine

103

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Abstract18 F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The α-melanocyte-stimulating hormone (α-MSH) receptor (melanocortin type 1 receptor [MC1R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, 18 F compounds have not been successfully developed for imaging the MC1R.Methods-In this study, an α-MSH analog, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH 2 (NAPamide), was radiolabeled with N-succinimidyl-4-18 F-fluorobenzoate ( 18 F-SFB). The resulting radiopeptide was evaluated as a potential molecular probe for small-animal PET of melanoma and MC1R expression in melanoma xenografted mouse models.Results-The binding affinity of 19 F-SFB-conjugated NAPamide, 19 F-FB-NAPamide, was determined to be 7.2 ± 1.2 nM (mean ± SD) using B16/F10 cells and 125 I-(Tyr 2 )-[Nle 4 ,D-Phe 7 ]-α-MSH [ 125 I-(Tyr 2 )-NDP] as a radio-ligand. The biodistribution of 18 F-FB-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high expression of MC1Rs and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Biodistribution experiments showed that tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of 18 F-FB-NAPamide were 1.19 ± 0.11 %ID/g and 0.46 ± 0.11 %ID/g, in B16/F10 and A375M xenografted melanoma at 1 h after injection, respectively. Furthermore, the B16/F10 tumor uptake was significantly inhibited by coinjection with excess α-MSH peptide (P < 0.05), indicating that 18 F-FB-NAPamide specifically recognizes the MC1R in living mice. Small-animal PET of 18 F-FB-NAPamide in mice bearing COPYRIGHT © 2007 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptB16/F10 and A375M tumors at 1 h after tail vein injection revealed good B16/F10 tumor-tobackground contrast and low A375M tumor-to-background ratios.Conclusion-18 F-FB-NAPamide is a promising molecular probe for α-MSH receptor-positive melanoma PET and warrants further study. Keywordsmelanoma; α-melanocyte-stimulating hormone; PET; imaging; 18 F Cutaneous malignant melanoma is one of the most lethal cancers. Its incidence is increasing rapidly, making it a significant public health problem in Europe and the United States (1,2). Although extensive research has been performed to develop novel strategies for systemic treatment of malignant melanoma, effective therapies are still not available. The most important approach for improvement of survival of patients with melanoma still remains early diagnosis, along with accurate staging of the extent of disease (3,4).Many molecular imaging agents have been evaluated for detection of melanoma.Currently, 18 F-FDG is widely used in staging melanoma. The sensitivity, specificity, and accuracy of 18 F-FDG PET for detecting recurrent melanoma range from 70% to 100% (3). However, when imaging patients with early-stage melanoma, whole-body 18 F-FDG PET shows ...

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“…One property of anti-CD22 that is considered a disadvantage for this purpose is that it is quite rapidly internalized and catabolized (Press et al, 1989;Shih et al, 1994a), which would diminish the amount of radiation delivered to the target cell. A conventional iodine radiolabel on iodotyrosine is rapidly released from the cell as iodotyrosine after Ab degradation in lysosomes (Geissler et al, 1991;Shih et al, 1994b). However, this disadvantage can potentially be overcome by the use of ''residualizing'' radiolabels, which are trapped within target cells after catabolism of the Ab to which they were conjugated.…”

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confidence: 99%

The advantage of residualizing radiolabels for targeting B-cell lymphomas with a radiolabeled anti-CD22 monoclonal antibody

et al. 1997

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CD22 antibodies (Abs) bound to B-cell lymphomas are known to be internalized and catabolized rapidly. Therefore, it would be expected that use of CD22 as a target for radioimmunotherapy should be enhanced by the use of ''residualizing'' radiolabels, which are trapped within the cell after catabolism of the Ab to which they had been conjugated. Our study was intended to evaluate this hypothesis using Ab LL2. In initial experiments, we found that LL2 binding was strongly temperature dependent, with approximately 15-fold greater binding at 37°C than at 0°C. A series of experiments suggested that this difference is due to a conformational change in the antigen at low temperature, so that the LL2 epitope is partially blocked. In vitro, residualizing labels-including 125 I-dilactitol tyramine and 111 In-DTPAwere retained by cells much longer than a conventional iodine label. In vivo, residualizing labels also showed a marked advantage in terms of uptake by Ramos B-cell lymphoma xenografts in nude mice. However, the absolute Ab uptake by xenografts was quite low, in comparison with results obtained with many carcinoma xenografts, which appears to be due in part to vascular properties of the B-cell lymphoma xenografts. Int.

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Intracellular catabolism of radiolabeled anti-CD3 antibodies by leukemic T cells

Cited by 75 publications

References 32 publications

Evaluation of Near Infrared Fluorescent Labeling of Monoclonal Antibodies as a Tool for Tissue Distribution

Evaluation of Near Infrared Fluorescent Labeling of Monoclonal Antibodies as a Tool for Tissue Distribution

Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled -Melanocyte-Stimulating Hormone Analog

The advantage of residualizing radiolabels for targeting B-cell lymphomas with a radiolabeled anti-CD22 monoclonal antibody

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