Pharmacokinetics and biodistribution of 177Lu-labeled multivalent single-chain Fv construct of the pancarcinoma monoclonal antibody CC49

Chauhan, Subhash C.; Jain, Maneesh; Moore, Erik; Wittel, Uwe A.; Li, Jing; Gwilt, Peter R.; Colcher, David; Batra, Surinder K.

doi:10.1007/s00259-004-1664-0

Cited by 30 publications

(28 citation statements)

References 20 publications

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“…For example, a tetravalent scFv CC49 radiolabeled with 177 Lu demonstrated blood concentration at 24 hours postinjection was 0.5 %ID/g and tumor uptake was 5.5 %ID/g, resulting in a tumor-to-blood value of 11.0, compared to our value of 16.0 determined for 111 InHuCC49⌬C H 2. 51 Pavlinkova et al reported that 125 I-labeled dimeric scFv CC49 constructs were rapidly cleared from the blood with 0.07 %ID/g and tumor concentration of 5.62 %ID/g at 24 hours postinjection, resulting in a tumor-to-blood ratio of 80.3. 45 Although the dimeric scFv in that study provided a higher tumor-to-blood ratio than that observed for 111 In-HuCC49⌬C H 2 in our study, overall tumor uptake was lower for the scFv construct (14.4 %ID/g versus 5.62 %ID/g).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Chinn

Morena

Santoro

et al. 2006

Cancer Biotherapy and Radiopharmaceuticals

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The primary limitation of IgG antibodies for radioimmunotherapy of solid tumors is their prolonged serum half-life, leading to dose-limiting bone marrow toxicity at doses providing inadequate radiation to the tumor. A humanized C(H)2 domain-deleted variant of the anti-TAG-72 antibody CC49 (HuCC49DeltaC(H)2) has faster blood clearance, compared to the IgG, while retaining tumor targeting. We compared the pharmacokinetics and tumor uptake of (111)In-HuCC49DeltaC(H)2 in BALB/c mice and a colon carcinoma (LS-174T) mouse xenograft with that of (111)In-labeled chimeric CC49 (cCC49), an antibody with pharmacokinetics similar to the humanized CC49 parent. Immuno-conjugates of HuCC49DeltaC(H)2 and cCC49 prepared with the (111)In chelator Mx-DTPA (1-isothiocyantobenzyl-3-methyldiethylenetriaminepentaacetic acid) retained low nM affinity and radiolabeling protocols provided greater than 95% radio-incorporation with (111)In while retaining greater than 80% immunoreactivity. Blood clearance of (111)In-HuCC49DeltaC(H)2 in BALB/c mice was monoexponential (t(1/2) 5.4 hours) and faster than (111)In-cCC49 (biexponential clearance; t1/2Delta 1.5 hours; t1/2beta 162 hours). The (111)In-HuCC49DeltaC(H)2 also cleared more rapidly from the blood in the murine xenograft. At 1 hour postinjection, blood concentrations for (111)In-HuCC49DeltaC(H)2 and (111)In-cCC49 were comparable (25.5 injected dose per g [%ID/g] and 21.3 %ID/g, respectively); tumor uptake for (111)In- HuCC49DeltaC(H)2 was 7.9 %ID/g, compared to 7.5 %ID/g for (111)In-cCC49. However, at 24 hours, blood concentration for (111)In-HuCC49DeltaC(H)2 was less than (111)In-cCC49 (0.9 %ID/g versus 5.2 %ID/g, respectively) with comparable tumor retention (14.4 %ID/g versus 19.0 %ID/g, respectively). Faster blood clearance of (111)In-HuCC49DeltaC(H)2 and tumor localization comparable to that of (111)In-cCC49 provided a fourfold improved tumor-to-blood ratio for (111)In-HuCC49DeltaC(H)2 at 24 hours postinjection.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Chinn

Morena

Santoro

et al. 2006

Cancer Biotherapy and Radiopharmaceuticals

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“…As the molecular size of the construct increases, the blood clearance rates are reduced and tumor uptake increases. A few constructs, such as the tetrabody (120 kD) described by Goel et al (61), have a blood clearance rate about 50 percent faster than IgG in mice, but with a similar tumor uptake, and studies with the 99m Tc-tetrabody suggest that even tumor/kidney ratios are favorable, but recent studies with 177 Lu-labeled tetrabodies showed a higher uptake in the kidneys than in the tumor (62,63). Thus, there is considerable diversity available at this time for antibodies with different targeting properties, but clinical studies will be required to determine which radionuclides would be appropriately matched with each construct, and if they will increase the therapeutic window for targeted radionuclide therapy.…”

Section: Recombinant Antibodiesmentioning

confidence: 96%

Advances in Radioimmunotherapy in the Age of Molecular Engineering and Pretargeting

Sharkey¹,

Goldenberg²

2006

Cancer Investigation

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Now that radioimmunotherapy is an approved method for the treatment of certain types of non-Hodgkin's lymphoma, investigators are turning to new approaches to further improve radionuclide targeting in hopes of expanding the use of this technology. A number of innovative recombinant proteins have been developed with more favorable pharmacokinetic and targeting properties than standard whole IgG, which conceivably could improve the therapeutic index for cancer treatment. Pretargeting methods also are coming of age, with preclinical and early clinical studies in a variety of cancers illustrating how this alternative approach can enhance the therapeutic window several-fold of what has been possible with directly radiolabeled IgG. This review will discuss some of these promising new developments.

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“…To keep the immunocompetence of antibody and simplify the labeling process, multiple labeling nuclides can be utilized. [4][5][6] Its application in tumor diagnosis and therapy is increasingly attended by researchers at home and abroad. For the present clinic, the majority of antibodies using RII are monoclonal; however, the experience shows that the monoclonal antibodies belong to the rodential heterogeneous protein and have the immunogenicity; therefore, the various degrees of human anti-mouse antibody reactions may happen in the patients' bodies, they decrease the efficiency of therapy and cause the toxic damages to the organ responsible for removal of antibodies [7] .…”

Section: IVmentioning

confidence: 99%

Radioimmunoimaging of 153Sm labeled anti-H-OV-5ScFv in nude mice of ovarian cancer

Chang

Yang

et al. 2011

Proceedings 2011 International Conference on Human Health and Biomedical Engineering

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to study the radioimmunoimaging of 153 Sm labeled 153 Sm-H-OV-5 ScFv and normal mice IgG in nude mice bearing human primary ovarian cancer with three-step pretargetting method, to provide the early diagnosis of ovarian cancer with a new method, and to form the experimental basis for clinical use. 6.5MBg/0.1mL labeled antibody is injected into the tail vein of each mouse. The SPECTs are performed at the 2nd, 4th, 16th, 24th hour after injection. The mice are killed in lots and the percent injected dosages of every gram of tissue (%ID/g) are measured at the 2nd, 4th, 16th, 24th. 153 Sm-H-OV-5 ScFv can be selectively accumulated in the tumor tissues, and the rate of ingestion is higher than 153Sm-IgG (p<0.05). In the nude mice bearing human ovarian cancer, 153 Sm-H-OV-5 ScFv has affinity to the over-expressed ovarian cancer single chain antibody H-OV-5. 153 Sm-H-OV-5 ScFv is promising to become the direct carrier of ovarian cancer diagnosis.

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Pharmacokinetics and biodistribution of 177Lu-labeled multivalent single-chain Fv construct of the pancarcinoma monoclonal antibody CC49

Cited by 30 publications

References 20 publications

Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Advances in Radioimmunotherapy in the Age of Molecular Engineering and Pretargeting

Radioimmunoimaging of 153Sm labeled anti-H-OV-5ScFv in nude mice of ovarian cancer

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Pharmacokinetics and biodistribution of 177Lu-labeled multivalent single-chain Fv construct of the pancarcinoma monoclonal antibody CC49

Cited by 30 publications

References 20 publications

Pharmacokinetics and Tumor Localization of111In-Labeled HuCC49ΔCH2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Pharmacokinetics and Tumor Localization of111In-Labeled HuCC49ΔCH2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Advances in Radioimmunotherapy in the Age of Molecular Engineering and Pretargeting

Radioimmunoimaging of 153Sm labeled anti-H-OV-5ScFv in nude mice of ovarian cancer

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Product

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Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft

Pharmacokinetics and Tumor Localization of¹¹¹In-Labeled HuCC49ΔC_H2 in BALB/c Mice and Athymic Murine Colon Carcinoma Xenograft