Biodistribution and localization of iodine-131 labeled metuximab in patients with hepatocellular carcinoma

Zhang, Zheng; Bian, Huijie; Feng, Qiang; Li, Mi; Mo, Tingshu; Kuang, Anren; Tan, Tianwei; Li, Yun‐Chun; Lu, Wusheng; Zhang, Yang; Zhang, Min; Tian, Rong; Chen, Zhi‐Nan; Zhu, Ping

doi:10.4161/cbt.5.3.2431

Cited by 32 publications

(45 citation statements)

References 7 publications

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“…We had generated the 131 I-labeled Metuximab [trade name LICARTIN; generic name Iodine ( 131 I) Metuximab Injection] for in vivo injection. The pharmacokinetic characteristics and safety of the antibody and its radiolabeled conjugate had been determined both in vivo and in clinic (14,16,(19)(20)(21). LICARTIN was approved to be a new drug for clinical therapy of primary HCC patients by China State Food and Drug Administration (no.…”

Section: Introductionmentioning

confidence: 99%

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu¹,

Xu²,

Zhang³

et al. 2007

Molecular Cancer Research

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144

134

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CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb18G/CD147 gene silence in HCC cells significantly decreased the secretion of matrix metalloproteinase (MMP) and the invasive potential of HCC cells (P < 0.001). MMP silence in HCC cells also significantly suppressed the invasion of the cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P < 0.001). Blocking the HAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. 131 I-labeled HAb18 F(ab ¶) 2 (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P < 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPs, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/ CD147 in antimetastasis and recurrence therapy of HCC.

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Section: Introductionmentioning

confidence: 99%

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu¹,

Xu²,

Zhang³

et al. 2007

Molecular Cancer Research

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144

134

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“…12 Therefore, the RIT agents were tentatively administrated locally through the tumor supply blood vessel and some clinical studies using RIT ( 131 I-Metuximab administrated through hepatic artery intubation) for hepatocellular carcinoma showed promising efficacy. [29][30][31][32] However, the T/ NT was observed to be only 0.7-2.7. 30,31 If the T/NT can be improved, the tumor response will be more encouraging.…”

Section: Zheng Et Almentioning

confidence: 99%

“…[29][30][31][32] However, the T/ NT was observed to be only 0.7-2.7. 30,31 If the T/NT can be improved, the tumor response will be more encouraging. In addition, in the treatment of hepatic metastases with RFA before 131 I-chTNT-1/B infusion, Anderson et al reported that an average target to the background ratio of 2.9 (ranged from 1.3 to 6.0) was observed at the 3th day after 131 I-chTNT-1/B infusion.…”

Section: Zheng Et Almentioning

confidence: 99%

Radiofrequency Ablation Before Intratumoral Injection of ¹³¹I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX₂ Tumor

Zheng

Lu³

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Purpose: This study was aimed to investigate whether the tumor necrosis induced by radiofrequency ablation (RFA) can improve the ratio of tumor-to-normal tissue (T/NT) after intratumoral injection of 131 I-chTNT. Materials and Method: Eighteen New Zealand rabbits bearing VX 2 tumor on the thigh were randomly divided into two treatment groups (control group: intratumoral injection of 131 I-chTNT alone; RFA group: RFA + intratumoral injection of 131 I-chTNT 3 days after RFA) and each group was further divided into three subgroups I, II, and III (1-2 cm, 2-3 cm, and 3-4 cm in maximum diameter, respectively), by the tumor size. SPECT was performed to evaluate the T/NT on days 1, 8, and 15 after 131 I-chTNT injection. Results: After treatment, all rabbits underwent the SPECT whole-body scan and the T/NT was analyzed. The results showed that T/NT in the RFA group (55.45 -41.83) was significantly higher compared with the control group (7.23 -5.61) (F = 18.89, p = 0.001). Meanwhile, a linear ascending trend was found for T/NT in the RFA group along with the follow-up time (r = 0.47, p = 0.01). The tumor size or the dose of 131 I-TNT injection had no significant effect on the variation of T/NT in both groups ( p > 0.05). Conclusion: RFA before intratumoral injection of 131 I-chTNT can dramatically improve T/NT, demonstrating the potential application of this combination therapy.

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“…The residues were replaced by their human counterparts, the change did not affect the conformational stability and the antigen binding activity of the antibody, and the antigenic epitopes presented were eliminated. The construction of a humanized (HAb18-huscFv) 2 -Fc fusion protein was described. We humanized HAb-18scFv gene and substituted for the linker with (Gly 4 Ser) 4 , which was then spliced with the Fc region of human IgG1.…”

Section: 12mentioning

confidence: 99%

“…Licartin has been found to be able to concentrate in the tumor region, and it is safe and effective for the treatment of HCC. 1,2 As a promising new drug for preventing post-orthotopic liver transplantation (OLT) tumor recurrence in advanced HCC patients, 3 it gained approval for clinical therapy of primary HCC from China State Food and Drug Administration (Registration No. S20050039) in April, 2005.…”

Section: Introductionmentioning

confidence: 99%

A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity

Zhu

Yang²,

Yang³

et al. 2009

Cancer Biology & Therapy

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[ 131 I]Metuximab injection (Licartin) was an efficient therapeutic anti-hepatocellular carcinoma (HCC) radioimmunological agent generated by labeling 131 I with the murine monoclonal antibody fragment HAb18-F(ab') 2 but human anti-mouse antibody (HAMA) response in some patients after administration limited its clinical use. To reduce the immunogenicity of murine antibody, we attempted to humanize HAb18 by variable domain resurfacing based on the three-dimensional structure of Fv fragment. Considering the surface accessibility of non-human like framework residues and the potential to form a molecular hydrogen bond within the context of the homology modeled Fv of HAb18, three residues in a single chain fragment of antibody variable region of HAb18 (HAb18scFv) were replaced by their human counterparts. We fabricated a humanized version of HAb18scFv, HAb18-huscFv, to the human IgG1Fc fragment to form (HAb18-huscFv) 2 -Fc. The reactivity of (HAb18-huscFv) 2 -Fc to the serum of patients with HAMA response was decreased while its specificity and similar binding activity (K D = 1.5 x 10 -9 M) were retained compared with its parental antibody. In addition, this antibody is an efficient mediator of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These results suggest (HAb18-huscFv) 2 -Fc could be a more efficient antibody fragment with less immunogenicity and additional cytotoxicity function.

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Biodistribution and localization of iodine-131 labeled metuximab in patients with hepatocellular carcinoma

Cited by 32 publications

References 7 publications

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Radiofrequency Ablation Before Intratumoral Injection of ¹³¹I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX₂ Tumor

A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity

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Biodistribution and localization of iodine-131 labeled metuximab in patients with hepatocellular carcinoma

Cited by 32 publications

References 7 publications

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Radiofrequency Ablation Before Intratumoral Injection of 131I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX2 Tumor

A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity

Contact Info

Product

Resources

About

Radiofrequency Ablation Before Intratumoral Injection of ¹³¹I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX₂ Tumor