Acta Oncologica

1993

DOI: 10.3109/02841869309096139

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Radioimmunotherapy with⁹⁰Y-Labeled Monoclonal Antibodies in a Nude Mouse Ovarian Cancer Model

¹

,

²

,

Sven‐Erik Strand

³

et al.

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Cited by 10 publications

(3 citation statements)

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“…This is par ticularly true when genetically engineered cell-or tissuespecific macromolecules are administered, such as anti body-targeted drugs, toxins, or radionuclides [17,18], 'immuno'-liposomes [19], or cytokine gene-modified tu mor vaccines [20,21]. Indeed, the endothelium with its host-specific antigenicity may have functioned as an ef- fective barrier to antibody-targeted macromolecules in an ovarian cancer xenograft model (in which intratumoral administration of a 90Y-labeled monoclonal antibody yielded much better antitumor activity when compared to intraperitoneal or intravenous administration) [22], or in a colorectal carcinoma xenograft model (in which intra peritoneal injection of the monoclonal antibody 17-lA showed significant antitumor activity, which was entirely lost when treatment was delayed until the tumor cells had formed vascularized nodules) [23].…”

Section: Discussionmentioning

confidence: 99%

Microvascular Endothelium of Human Tumor Xenografts Expresses Mouse (= Host) CD31

Lehr¹,

et al. 1997

Int J Microcirc

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Background: Human malignant tumors grown as xenografts in immunocompromised animals have been used extensively to study tumor growth and tumor response to therapy. The endothelium functions as an effective barrier between the intravascular space and the tumor cells. In a previous study we used species-specific monoclonal antibodies against endothelial cell adhesion molecules to demonstrate the host origin of the endothelium in xenotrans-planted pancreatic islet grafts [Am J Pathol 1995;146:1397-1405]. We now investigated in this study whether the vascular endothelium of different xenografted human malignant tumors expresses mouse (= host)- or human (= graft)-specifïc CD31 (platelet endothelial cell adhesion molecule, PECAM-1) adhesion molecules. Methods and Results: Cultured human prostate, kidney, and colon cancer cells (passages 15-17) were transplanted subcutaneously into 8-week-old athymic nude mice and removed after another 8 weeks. The avidin biotin peroxidase method was utilized on frozen sections to demonstrate that the endothelium of the vasculature of all three human xenografts expressed mouse (= host)-specific CD31, but not human (= graft)-specific CD31. Conclusion: The presence between the intravascular space and the human tumor cells of a mouse-derived endothelium, expressing mouse-specific antigens, needs to be taken into careful consideration when evaluating results of antitumor therapies in these animal models. This caveat pertains particularly to the study of novel cell- or tissue-specific treatment modalities, such as antibody-targeted drugs, toxins or radionuclides, ‘immuno’-liposomes, or tumor vaccines.

“…This is par ticularly true when genetically engineered cell-or tissuespecific macromolecules are administered, such as anti body-targeted drugs, toxins, or radionuclides [17,18], 'immuno'-liposomes [19], or cytokine gene-modified tu mor vaccines [20,21]. Indeed, the endothelium with its host-specific antigenicity may have functioned as an ef- fective barrier to antibody-targeted macromolecules in an ovarian cancer xenograft model (in which intratumoral administration of a 90Y-labeled monoclonal antibody yielded much better antitumor activity when compared to intraperitoneal or intravenous administration) [22], or in a colorectal carcinoma xenograft model (in which intra peritoneal injection of the monoclonal antibody 17-lA showed significant antitumor activity, which was entirely lost when treatment was delayed until the tumor cells had formed vascularized nodules) [23].…”

Section: Discussionmentioning

confidence: 99%

Microvascular Endothelium of Human Tumor Xenografts Expresses Mouse (= Host) CD31

Lehr¹,

et al. 1997

Int J Microcirc

View full text Add to dashboard Cite

Background: Human malignant tumors grown as xenografts in immunocompromised animals have been used extensively to study tumor growth and tumor response to therapy. The endothelium functions as an effective barrier between the intravascular space and the tumor cells. In a previous study we used species-specific monoclonal antibodies against endothelial cell adhesion molecules to demonstrate the host origin of the endothelium in xenotrans-planted pancreatic islet grafts [Am J Pathol 1995;146:1397-1405]. We now investigated in this study whether the vascular endothelium of different xenografted human malignant tumors expresses mouse (= host)- or human (= graft)-specifïc CD31 (platelet endothelial cell adhesion molecule, PECAM-1) adhesion molecules. Methods and Results: Cultured human prostate, kidney, and colon cancer cells (passages 15-17) were transplanted subcutaneously into 8-week-old athymic nude mice and removed after another 8 weeks. The avidin biotin peroxidase method was utilized on frozen sections to demonstrate that the endothelium of the vasculature of all three human xenografts expressed mouse (= host)-specific CD31, but not human (= graft)-specific CD31. Conclusion: The presence between the intravascular space and the human tumor cells of a mouse-derived endothelium, expressing mouse-specific antigens, needs to be taken into careful consideration when evaluating results of antitumor therapies in these animal models. This caveat pertains particularly to the study of novel cell- or tissue-specific treatment modalities, such as antibody-targeted drugs, toxins or radionuclides, ‘immuno’-liposomes, or tumor vaccines.

“…Therefore, following systemic administration, the amount of radioactivity delivered to the tumour by a radiolabelled monoclonal antibody or other targeting ligand may be insufficient to effectively eradicate solid tumours. It is possible to increase the amount of radioactivity that specifically reaches the tumour by direct intratumoural injection 5 , 6 . However, such an approach is most applicable to superficial tumours, which account for a minority of solid tumours.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of ¹¹¹In-Labelled EGF-Au-PEG Nanoparticles in EGFR-Positive Tumours is Enhanced by Coadministration of Targeting Ligand

Song¹,

Able²,

et al. 2017

Nanotheranostics

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The successful use of targeted radionuclide therapy in the treatment of solid tumours may be limited by radioresistance, which necessitates delivery of a high dose of radioactivity. Nanoparticle (NP)-based delivery systems possess a large surface area for attachment of radioisotopes and so offer a solution to this challenge. However, tumour uptake may be limited by rapid hepatic clearance of NP via the mononuclear phagocyte system. Liver uptake is further compounded when epidermal growth factor (EGF) is used as a targeting ligand, as EGF-tagged NP bind the EGF receptor (EGFR), which is expressed to a moderate extent by hepatocytes. This report describes an indium-111 (111In)-labelled PEGylated EGF-tagged gold (Au) NP (111In-EGF-Au-PEG) and an effective strategy of coadministration of targeting ligand to address these issues. Direct attachment of EGF to the surface of Au NP did not compromise surface coating with long-chain PEG. In vitro experiments showed that 111In-EGF-Au-PEG targets EGFR-positive cancer cells (MDA-MB-468): >11% of radioactivity was internalised after incubation for 4 h. In in vivo studies accumulation of NP was observed in MDA-MB-468 xenografts and tumour uptake was enhanced by the coadministration of 15 µg of the unlabelled targeting ligand, EGF, to block hepatic EGFR. Uptake was 3.9% versus 2.8% injected dose/g (%ID/g) of tumour tissue with and without unlabelled EGF, respectively. Coadministration of EGF reduced liver uptake by 25.95% to 7.56 %ID/g. This suggests that the coadministration of unlabelled targeting ligand with radiolabelled PEGylated NP offers a promising strategy for targeting EGFR-positive cancer and for minimising liver uptake.

“…В последнее десятилетие большое количество публикаций по радионуклидной терапии посвящено использованию 90 Y. В открытой печати имеются сведения о синтезе и оценке функциональной пригодности для терапии новых РФЛП с 90 Y, представляющих собой меченые пептиды и моноклональные антитела [9,10].…”

Section: Introductionunclassified

Analysis of Current Rules and Regulations for Preclinical Studies of Radiopharmaceuticals

Lunev,

Petrosova,

Ternovskaya

et al. 2024

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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SCIENTIFIC RELEVANCE. Owing to specific aspects of their development and use, radiopharmaceuticals require separate rules and regulations for preclinical studies. However, current legislation and regulations on the organisation and conduct of preclinical studies of radiopharmaceuticals contain a number of contradictions and need improvement.AIM. This review aimed to analyse the rules and regulations governing preclinical studies of radiopharmaceuticals in the Russian Federation and abroad.DISCUSSION. The regulatory requirements for preclinical studies of radiopharmaceuticals that are conducted by specialised institutions in Russia and abroad have several shortcomings and inconsistencies. Laboratories working with animals and open sources of ionising radiation should prioritise regulations related to radiation safety. Radiation safety requirements should be in line with the sanitary standards and practical guidelines used in preclinical studies. This review covers the specific aspects of conducting preclinical studies of therapeutic and diagnostic radiopharmaceuticals. According to the review results, international guidelines for preclinical studies of radiopharmaceuticals focus on systematising the applicable requirements and aim at providing a consistent approach to preclinical studies to reduce the conduct of studies that are not informative for a specific radiopharmaceutical product.CONCLUSIONS. Radiation safety requirements should be harmonised with international guidelines. Methodological recommendations and local regulations should be developed and approved to facilitate the resolution of regulatory issues related to the organisation and conduct of preclinical studies of radiopharmaceuticals. Many medical, social, technical, and administrative issues need addressing at the inter-institutional and/or national level.

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