Global HDO uptake in human glioma xenografts is related to the perfused capillary distribution

Sanden, B.P.J. van den; Zandt, René in ‘t; Hoofd, Louis; Graaf, R.M. de; Nicolay, Klaas; Rijken, P.F.J.W.; Kogel, Albert J. van der; Heerschap, Arend

doi:10.1002/(sici)1522-2594(199909)42:3<479::aid-mrm10>3.0.co;2-h

Cited by 9 publications

(3 citation statements)

References 20 publications

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“…We previously measured the fast diffusion component of water in RIF‐1 tumors to be 1.1 × 10 ‐9 m 2 /second (30), and typically expect subcutaneous tumors to have a diffusion coefficient D in the range 0.7–1.8 × 10 ‐9 m 2 /second (31, 32). Using the above calculated Δχ and the average ΔR 2 * (Table 2), we estimate the fractional blood volume to be 8% for the GH3 and 2% for the RIF‐1.…”

Section: Discussionmentioning

confidence: 99%

Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

Robinson

Rijken²,

Howe

et al. 2003

Magnetic Resonance Imaging

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Purpose:To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O 2 /5% CO 2 ) breathing observed with different tumor types. Materials and Methods:Susceptibility contrast-enhanced MRI using the exogenous blood pool contrast agent NC100150 to determine blood volume and vessel size, and immunohistochemical-derived morphometric parameters, were determined in GH3 prolactinomas and RIF-1 fibrosarcomas, both grown in mice, which exhibited very different BOLD responses to carbogen.Results: Administration of NC100150 increased the R 2 * and R 2 rates of both tumor types, and indicated a significant four-fold larger blood volume in the GH3 tumor. The ratio ⌬R 2 */⌬R 2 showed that the capillaries in the GH3 were two-fold larger than those in the RIF-1, in agreement with morphometric analysis. Carbogen breathing induced a significant 25% decrease in R 2 * in the GH3 prolactinoma, whereas the response in the RIF-1 fibrosarcoma was negligible. Conclusion:Low blood volume and small vessel size (and hence reduced hematocrit) are two reasons for the lack of R 2 * change in the RIF-1 with carbogen breathing. BOLD MRI is sensitive to erythrocyte-perfused vessels, whereas exogenous contrast agents interrogate the total perfused vascular volume. BOLD MRI, coupled with a carbogen challenge, provides information on functional, hemodynamic tumor vasculature.

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Section: Discussionmentioning

confidence: 99%

Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

Robinson

Rijken²,

Howe

et al. 2003

Magnetic Resonance Imaging

Self Cite

129

141

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“…The mean intravascular transit time and the standard deviation of the transit time are estimated for each tissue, in addition to the other haemodynamic parameters of blood flow, extraction coefficient of the tracer and rate constant for the clearance of the tracer. Our motivation for developing this model is the fact that vascular architecture in cancerous tissue is drastically different from that in normal tissue (Jain 1988, Bigler et al 1993, Montironi et al 1996, van der Sanden et al 1999, Goldbrunner et al 1999, Tufto and Rofstad 1999, which may have important implications for tumour growth and malignant progression. We have applied the model for blood flow measurement in prostate cancer using contrast enhanced dynamic x-ray computed tomography (CT) scanning.…”

Section: Introductionmentioning

confidence: 99%

The inclusion of capillary distribution in the adiabatic tissue homogeneity model of blood flow

et al. 2001

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We have developed a non-invasive imaging tracer kinetic model for blood flow which takes into account the distribution of capillaries in tissue. Each individual capillary is assumed to follow the adiabatic tissue homogeneity model. The main strength of our new model is in its ability to quantify the functional distribution of capillaries by the standard deviation in the time taken by blood to pass through the tissue. We have applied our model to the human prostate and have tested two different types of distribution functions. Both distribution functions yielded very similar predictions for the various model parameters, and in particular for the standard deviation in transit time. Our motivation for developing this model is the fact that the capillary distribution in cancerous tissue is drastically different from in normal tissue. We believe that there is great potential for our model to be used as a prognostic tool in cancer treatment. For example, an accurate knowledge of the distribution in transit times might result in an accurate estimate of the degree of tumour hypoxia, which is crucial to the success of radiation therapy.

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“…The cellular compartment was included in the extravascular compartment, since water diffusion across the cell membrane is faster (35-37) than water perfusion (38,39), thus:…”

Section: Theoretical Backgroundmentioning

confidence: 99%

Parametric imaging of tumor perfusion using flow‐ and permeability‐limited tracers

Bogin

Margalit

Mispelter³

et al. 2002

Magnetic Resonance Imaging

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Purpose: To quantitatively evaluate the spatial distribution of flow-and permeability-limited perfusion in MCF7 human breast cancer tumors orthotopically implanted in CD1-NU mice. Materials and Methods:Flow-limited perfusion was derived from 2 H-MRI recorded before and after infusion of deuterated water. Permeability-limited perfusion was evaluated from GdDTPA-enhanced 1 H-MRI. Results:The dominant processes in tumor perfusion, namely blood flow and capillary permeability, were mapped in orthotopically implanted MCF7 human breast cancer tumors. The dynamic data were processed according to physiological models, yielding parametric maps of intravascular volume fraction, water perfusion rate, GdDTPA permeability rate constant, and extracellular volume fraction accessible to GdDTPA. The maps exhibited the heterogeneous distribution of each perfusion parameter. Most of the tumor tissue (Ն95%) was perfused with HDO, while Gd-DTPA was perfused in only about 50% of it. In most loci the perfusion rate was limited by capillary permeability to Gd-DTPA. Conclusion:The results demonstrated the instructive value of tracers with different properties used in conjunction to achieve a deeper understanding of tumor perfusion capacity. This study offers tools for the accurate, noninvasive evaluation of drug delivery efficacy. THE DEVELOPMENT OF A FUNCTIONING vascular network requires coordination between different cell types and is regulated by multiple growth factors, cytokines, kinases, and other growth regulatory proteins (Refs. 1 and 2, and references cited therein). These modulators constantly stimulate the formation of tumor neovascularization, and therefore maturation of the vessel network is rarely complete (3). Moreover, the architecture of the capillary bed in tumors is complex and tortuous, the capillary walls are leaky, and interstitial fluid pressure is elevated-hence tumor perfusion is irregular (Ref. 4 and references cited therein). These unique properties of tumor vasculature, and the dependency of tumor growth on this vasculature, make it an appropriate target for anticancer therapies (5,6). Thus, quantitative assessment of tumor perfusion plays a critical role in measuring the success of antivasculature therapy. Evaluation of tumor perfusion is also important in predicting the efficiency of drug delivery to its site of action.Tissue perfusion involves two major processes: blood flow and capillary permeability. An additional physiological parameter dominating tissue perfusion is the volume and surface area of the capillaries occupying the tissue. The dynamic nature of these processes implies that they should be monitored in vivo with the application of noninvasive methods such as dynamic magnetic resonance imaging (MRI).An appropriate tracer for monitoring flow-limited perfusion is water, since the net capillary permeability to water is considered to be much higher than its flow. Deuterium-labeled water is MR-detectable, with little toxicity to the host (7). Accordingly, deuterated water has been used as a tracer s...

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Global HDO uptake in human glioma xenografts is related to the perfused capillary distribution

Cited by 9 publications

References 20 publications

Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

The inclusion of capillary distribution in the adiabatic tissue homogeneity model of blood flow

Parametric imaging of tumor perfusion using flow‐ and permeability‐limited tracers

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