177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

Zacchetti, Alberto; Coliva, Angela; Luison, Elena; Seregni, Ettore; Bombardieri, Emilio; Giussani, A.; Figini, Mariangela; Canevari, Silvana

doi:10.1016/j.nucmedbio.2009.05.004

Cited by 28 publications

(20 citation statements)

References 26 publications

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“…The radiolabeling yield and specific activities obtained in this study were higher than in previous reports for similar conjugates. 4,29,[31][32][33][34][35] Comparable specific activities were obtained by Michel et al 33 The higher radiolabeling yield and specific activities obtained in this study are mainly due to the high modification of h-R3 by DOTA groups and the use of 177 Lu n.c.a. Statistically significant differences ( p < 0.05) in the radiolabeling yield were found between conjugates with different DOTA/h-R3 molar ratios when carrier-added 177 Lu was used for radiolabeling; increasing DOTA/h-R3 ratio from 9 to 13 increases the radiolabeling yield and specific activities, unlike from 13 to 15 ratios.…”

Section: Discussionsupporting

confidence: 52%

Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Beckford-Vera

Eigner

Beran

et al. 2011

Cancer Biotherapy and Radiopharmaceuticals

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Section: Discussionsupporting

confidence: 52%

Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Beckford-Vera

Eigner

Beran

et al. 2011

Cancer Biotherapy and Radiopharmaceuticals

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“…The maximal AFRA-DFM-injected doses were selected according to previous experience with 131 I-labeled antibodies by us (20) and others (23) and taking into consideration both operator exposure and possible initial cross-irradiation between animals. Possible animal death due to irradiation (monitored in non-tumor-bearing mice) and body weight were controlled on a regular basis.…”

Section: In Vivo Toxicitymentioning

confidence: 99%

“…For evaluation of radioimmunotherapy activity and specificity, the 2 AFRA-DFM human fragments were tested after systemic administration in the subcutaneous model system previously used to evaluate the efficacy of the anti-FR 131 I-MOv18 antibody (20). Details of the experiments are reported in Table 1, and representative curves are shown in Figure 2.…”

Section: Systemic Treatmentmentioning

confidence: 99%

“…In the past, we have produced different human antibodies against FR using phage display, starting either from a naïve library (19) or from a library from patients with a previous history of ovarian cancer (4) using guided selection, which allows for isolation of an antibody with the same specificity as the preexisting murine antibody. In particular, several antibody fragments have been isolated, one of which was genetically and chemically manipulated to obtain a dimer, namely AFRA-DFM5.3, with characteristics suitable for clinical applications (4,20).…”

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confidence: 99%

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Antitumor Effects of a Human Dimeric Antibody Fragment ¹³¹I-AFRA-DFM5.3 in a Mouse Model for Ovarian Cancer

et al. 2011

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AFRA-DMF5.3 is a human antibody fragment that, as a dimer, specifically binds to the a-folate receptor (FR) on ovary cancer cells. Pharmacokinetic and biodistribution parameters of 131 I-AFRA-DFM5.3 after intravenous administration in animal models support its potential therapeutic use. We evaluated its preclinical specificity and therapeutic efficacy in tumor models. Methods: A negative control, AFRA-DFM6.1, was obtained by protein engineering. The activity and specificity of 131 I-AFRA-DFMs were evaluated by systemic administration (intravenous) in subcutaneous tumor xenograft-bearing nude mice. Pharmacokinetics, biodistribution, and efficacy were assessed by intraperitoneal administration of 131 I-AFRA-DFM5.3 in nude mice bearing 2 different intraperitoneal ovarian carcinoma xenografts. Treatments were tested at different doses and as single or double administrations 1 wk apart. Results: In subcutaneous models, 131 I-AFRA-DFM5.3, but not the negative control, was found to reside on FR-positive tumor masses and significantly reduced tumor growth. In intraperitoneal models, early accumulation on free-floating clumps of ovarian cancer cells and solid peritoneal masses was evident after 1 h, and tumor uptake was stable for up to 3 h. The high tumor uptake determined the efficacy of 131 I-AFRA-DFM5.3. The best antitumor activity, with more than 50% of treated animals cured, was achieved with 2 locoregional treatments of intraperitoneally growing tumors on days 2 and 9. Conclusion: These results suggest that radioimmunotherapy with 131 I-AFRA-DFM5.3 is feasible and leads to significantly prolonged survival. These preclinical data provide the basis for the rationale design of therapeutic treatments of ovarian cancer patients with a radiolabeled anti-FR antibody fragment.

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“…Based on the specificity of the carrier and its affinity for the tumor, radionuclides are released in a targeted manner to focus their lethal effect on tumor cells. This is a non-toxic treatment method for the host (4,5). RIT is becoming a focus of study internationally.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic study of 131I-labeled CA215 antibody on an animal model of estrogen-resistant OC-3-VGH ovarian cancer

Liu

Xie

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to explore the inhibitory effect of 131 I-labeled ovarian cancer antigen 215 ( 131 I-CA215) antibody on human OC-3-VGH ovarian cancer. A subcutaneous transplanted tumor model of estrogen-resistant human OC-3-VGH ovarian cancer in nude mice was established. The model mice were randomly divided into seven groups, which were the negative control (NC), positive control (PC; 60 mg/kg cyclophosphamide), high-dose CA215 antibody (HA; 10 mg/kg), low-dose CA215 antibody (LA; 2 mg/kg), high-dose IntroductionOvarian cancer seriously impedes the reproductive health of females. Data from the American Cancer Society show that ovarian cancer is the ninth most common type of cancer in females (excluding skin cancer). It ranks fifth as the cause of cancer mortality in females. In 2013, it was estimated that there were ~22,240 new cases of ovarian cancer and ~14,230 individuals succumbed to this cancer (1). In China, ovarian cancer is the third most frequent cause of mortality among females (2). However, due to factors including environmental factors and drug treatment, the cell types and subtypes of ovarian cancer are increasing. For example, the OC-3-VGH cell line is a line of ovarian cancer that seldom expresses the estrogen receptor (3), and is insensitive to estrogen. The OC-3-VGH cell line was first successfully isolated in Taiwan (3). However, few studies have been conducted on this tumor type. The successful establishment of an animal model of OC-3-VGH would provide a drug study platform for the treatment of patients with estrogen-resistant ovarian cancer.In radioimmunotherapy (RIT), a highly specific pro-tumor substance is used as a carrier. Based on the specificity of the carrier and its affinity for the tumor, radionuclides are released in a targeted manner to focus their lethal effect on tumor cells. This is a non-toxic treatment method for the host(4,5). RIT is becoming a focus of study internationally. However, studies on RIT of ovarian cancer are limited (6). In the present study, a xenograft model of human OC-3-VGH ovarian cancer in nude mice was established to investigate the in vivo tumor inhibitory effect of 131 I-labeled ovarian cancer antigen 215 ( 131 I-CA215) antibody. This may provide the basis of further drug studies and a theoretical basis for the use of radiation therapy in the treatment of patients with estrogen-resistant ovarian cancer. Materials and methods Materials

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177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

Cited by 28 publications

References 26 publications

Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Antitumor Effects of a Human Dimeric Antibody Fragment ¹³¹I-AFRA-DFM5.3 in a Mouse Model for Ovarian Cancer

Pharmacodynamic study of 131I-labeled CA215 antibody on an animal model of estrogen-resistant OC-3-VGH ovarian cancer

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177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

Cited by 28 publications

References 26 publications

Preclinical Evaluation of 177Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Preclinical Evaluation of 177Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Antitumor Effects of a Human Dimeric Antibody Fragment 131I-AFRA-DFM5.3 in a Mouse Model for Ovarian Cancer

Pharmacodynamic study of 131I-labeled CA215 antibody on an animal model of estrogen-resistant OC-3-VGH ovarian cancer

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Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Preclinical Evaluation of ¹⁷⁷Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor–Overexpressing Tumors

Antitumor Effects of a Human Dimeric Antibody Fragment ¹³¹I-AFRA-DFM5.3 in a Mouse Model for Ovarian Cancer