Vascular volume and permeability of human and murine tumors grown in athymic mice

doi:10.1016/0304-3835(85)90004-7

Cancer Letters

Volume 27, Issue 1, May 1985, Pages 15-21

https://doi.org/10.1016/0304-3835(85)90004-7 Get rights and content

Abstract

^99mTc-labeled red blood cells have been used to measure tumor vascular volume (VV). When combined with the use of ¹²⁵I-labeled bovine serum albumin ([¹²⁵I]BSA) and ¹³¹I-labeled IgGs this method also provides the rapid simultaneous determination of tumor vascular permeability (VP). Using this technique the VV and VP of a human (Clouser) and a murine tumor (SL2) grown in athymic mice were determined. The relative VV were Clouser = SL2 ≥ skin > muscle. The relative VP of BSA and IgG were Clouser > SL2 = skin > muscle. These results may explain the differences observed in the accumulation of monoclonal antibodies in human and murine tumors grown in the athymic mouse.

References (6)

N.B. Ackerman et al.
Comparison of vascular permeability of tumors and liver host tissue
Bibl. Anat.
(1977)
F.K. Bauer et al.
Accumulation of homologous radioiodinated albumin in experimental tumors
D. Colcher et al.
Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody
Cancer Res.
(1983)

There are more references available in the full text version of this article.

Cited by (38)

Multiple uses of tumor necrosis therapy (TNT) for the treatment and imaging of solid tumors: Preclinical considerations and progress
2006, Update on Cancer Therapeutics
In an attempt to identify reagents that can elicit an effective anti-tumor immune response, we produced a panel of fusion proteins consisting of the tumor necrosis therapy (TNT) antibody and potent cytokines/chemokines. At the center of this approach is the TNT antibody, which has several important characteristics that make it an ideal delivery agent for immune modulators. These include its applicability to a wide range of human and animal cancers, its inability to bind normal tissues, its long retention time in tumors, and its ability to target necrotic regions in primary and metastatic lesions. Because of these attributes, TNT has been used to deliver radionuclides, immunostimulatory molecules, and vasopermeability agents to treat tumors. Moreover, TNT can be used with imaging to provide critical information concerning the effects of cytoreductive therapy early in the course of treatment and to demonstrate the ability of vasoactive antibody reagents to improve the uptake of drugs used for the treatment of cancer. To date over 250 patients have been treated with ¹³¹I-chTNT-3 demonstrating that all types of tumors can be targeted without significant uptake in normal tissues. TNT fusion proteins therefore have unique promise as second generation agents for the immunotherapy of solid tumors.
Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts
2001, Neoplasia
Several studies have linked vascular density, identified in histologic sections, to “metastatic risk.” Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenograffs preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF) expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P < .05, two-sided unpaired t test). The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.
In situ 19F MRS measurement of RIF-1 tumor blood volume: Corroboration by radioisotope-labeled [125I]-albumin and correlation to tumor size
1996, Magnetic Resonance Imaging
Tumor blood volume (TBV) is an important factor in the metabolism of a tumor and in its response to therapy. Until recently, the only methods to determine TBV were highly invasive and many involved radioisotopes. In this study, a perfluorocarbon (PFC) emulsion, Oxypherol, was monitored by ¹⁹F magnetic resonance spectroscopy (MRS). TBVs, as determined by ¹⁹F MRS of in situ and excised radiation-induced fibrosarcoma (RIF-1) tumors (n = 9), were strongly correlated with the TBV measured by a radioisotope labeled albumin method (slopes of 1.1 and 0.8 with R = 0.86 and 0.91, respectively, by linear regression). In general, the TBV as calculated from the in situ MRS measurements (n = 24) decreased from 28 to 5 ml/100 g tumor mass for tumors ranging in mass from 0.15 to 2 g. However, there was an indication of an initial increase of TBV in tumors smaller than 0.5 g.
Demonstration of differences in vascular permeability in experimental tumors by use of 19F magnetic resonance imaging
1994, Academic Radiology
Rationale and Objectives. In vivo assessment of tumor vascular permeability may provide useful information for chemotherapy treatment planning or for the assessment of treatment effectiveness. We aimed to assess vascular permeability in two tumor sublines as well as changes in vascular permeability with tumor growth by using ¹⁹F magnetic resonance imaging.
An emulsion of perfluorotributylamine was used as a tumor extravascular contrast agent for ¹⁹F MRI. The amount of emulsion that leaked into tumor interstitial space was analyzed qualitatively with imaging. A quantitative study of vascular permeability was done with a separate group of tumors by use of Evans blue dye.
One tumor type was more permeable to both perfluorotributylamine emulsion and Evans blue than was the second tumor type. The difference was attributed to a difference in surface area for exchange. In larger tumors of both types, pooling of large amounts of perfluorocarbon occurred and was assumed to be attributable to hemorrhage or blood flow stasis or both.
¹⁹F MRI is capable of demonstrating the permeability of tumor vessels to macromolecular substances.
The effect of antigen concentration, antibody valency and size, and tumor architecture on antibody binding in multicell spheroids
1991, International Journal of Radiation Applications and Instrumentation.
Intact IgG₁ and F(ab′)₂ anti-carcinoembryonic antigen antibodies penetrate human colon adenocarcinoma multicell spheroids much more slowly than Fab fragments and the molecular weight and the binding site valency appear to be the most important factor in determining the rate of penetration. The rate is also influenced considerably by the number of antigen binding sites per cell, with a high antigen concentration slowing penetration appreciably. The tumor cell architecture appears to have a minor effect on antibody penetration when compared to antibody size or antigen concentration.
Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology
2018, AAPS Journal

View all citing articles on Scopus

View full text

Article preview

Cancer Letters

Abstract

References (6)

Comparison of vascular permeability of tumors and liver host tissue

Bibl. Anat.

Accumulation of homologous radioiodinated albumin in experimental tumors

Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody

Cancer Res.

Cited by (38)

Multiple uses of tumor necrosis therapy (TNT) for the treatment and imaging of solid tumors: Preclinical considerations and progress

Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts

In situ <sup>19</sup>F MRS measurement of RIF-1 tumor blood volume: Corroboration by radioisotope-labeled [<sup>125</sup>I]-albumin and correlation to tumor size

Demonstration of differences in vascular permeability in experimental tumors by use of <sup>19</sup>F magnetic resonance imaging

The effect of antigen concentration, antibody valency and size, and tumor architecture on antibody binding in multicell spheroids

Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology

Research letterVascular volume and permeability of human and murine tumors grown in athymic mice

Abstract

Comparison of vascular permeability of tumors and liver host tissue

Bibl. Anat.

Accumulation of homologous radioiodinated albumin in experimental tumors

Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody

Cancer Res.

Research letter
Vascular volume and permeability of human and murine tumors grown in athymic mice