The use of vascular biomarkers and imaging studies in the early clinical development of anti‐tumour agents targeting angiogenesis

Drevs, Joachim; Schneider, Vesile

doi:10.1111/j.1365-2796.2006.01727.x

Cited by 43 publications

(42 citation statements)

References 24 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to identifying the maximal tolerable dose, determination of the optimal biological dose, reaching biological activity at lower doses, has become the main target in the early development of anti-angiogenic agents. This has been evaluated by different biomarker techniques (19). As a new standard in anti-tumor treatment, a better understanding of imaging in the treatment monitoring for anti-angiogenic agents is important.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, CDI was used as biomarker to measure blood flow in the tumor under treatment. Ultrasound is a favored modality for imaging angiogenesis because it does not expose patients to any significant risks, it is widely available, it can be repeated often, and it is mobile (19). In a study with PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor, CDI was used as surrogate marker in preclinical and clinical studies (4).…”

Section: Discussionmentioning

confidence: 99%

“…Biomarkers are important to establish biological activity and determine the optimal biological dose of novel therapies (19)(20)(21). In our study we investigated the influence of ZD6126 on tumor blood flow in afferent vessels to primary tumors by use of color Doppler imaging (CDI) ultrasound technique.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model

Medinger¹,

Esser²,

Soltau³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. ZD6126 is a vascular-disrupting agent that affects the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor cell necrosis. The present study evaluated the antitumor and antivascular activities of ZD6126 in the clinically relevant murine renal cell carcinoma (RENCA) model and also evaluated biological response to therapy using color Doppler imaging as biomarker. Mice were implanted with RENCA tumor cells (day 0) and established tumors were treated with ZD6126 (100 mg/kg i.p.) or vehicle with repeated intermittent doses on day 10, 14 and 18. ZD6126 treatment led to a significant reduction in tumor size and was associated with extensive tumor necrosis and a reduction in tumor blood flow versus controls. MVD increased with intermittent treatment (day 10, 14 and 18). In an additional study, animals were treated at day 19 and quantitative three-dimensional microvascular corrosion casting was performed to enable detailed assessment of the tumor vascular architecture. Corrosion casting showed that tumor vessel architecture is affected by treatment, whereas pre-existing vessels in control tissues are practically not affected. Inter-vessel and inter-branch distances as well as vessel diameters are influenced by treatment. In conclusion, ZD6126 showed potent antitumor efficacy in the RENCA model and our data suggest that decrease in tumor blood flow may be a useful surrogate marker of treatment effect.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model

Medinger¹,

Esser²,

Soltau³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…2,3 The proliferation of new blood vessels, originating from the existing vascular system, is needed both for tumor growth and metastatic dissemination. [4][5][6] Monoclonal antibodies, such as bevacizumab, targeting vascular endothelial growth factor to inhibit tumoral angiogenesis, suppress tumor growth. Such targeted drugs are increasingly used in combination with standardized platinum-based chemotherapy.…”

Section: Results: According To Biopsy 37 Patients Had Nsclc (22 Adenmentioning

confidence: 99%

“…17,18 Functional parameters, derived from the assessment of peak tumor enhancement over time in the tissue during the CTP scan, give information about blood volume (BV), blood flow (BF), and mean transit time (MTT) within the network of tumoral neovascularity, as well as the rate of abnormal leakage into the extracellular space, due to the vascular hyperpermeability in the abnormal neovessel wall. 5,19 One of the first applications for the assessment of lung lesions with CTP was pulmonary nodules, particularly in comparison with 18 F-fluoro-2-deoxy-D-glucose positron emission tomography/ CT (PET/CT). 20 Cutoff values have been defined for several CTP parameters to differentiate benign from malignant pulmonary nodules, with lower perfusion index (PI) and higher BF and BV obtained in malignancy.…”

Section: Results: According To Biopsy 37 Patients Had Nsclc (22 Adenmentioning

confidence: 99%

Assessment of Bronchial and Pulmonary Blood Supply in Non-Small Cell Lung Cancer Subtypes Using Computed Tomography Perfusion

Nguyen-Kim¹,

Frauenfelder²,

Strobel³

et al. 2015

Investigative Radiology

View full text Add to dashboard Cite

OBJECTIVES: The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). MATERIALS AND METHODS: A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. RESULTS: According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). CONCLUSIONS: The known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

show abstract

Molecular Pathology in Oncology Target and Drug Discovery

Ryseck

Attar

Lorenzi

et al. 2008

Molecular Pathology in Drug Discovery and Development

View full text Add to dashboard Cite

The use of vascular biomarkers and imaging studies in the early clinical development of anti‐tumour agents targeting angiogenesis

Abstract: Abstract. Drevs J, Schneider

Cited by 43 publications

References 24 publications

Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model

Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model

Assessment of Bronchial and Pulmonary Blood Supply in Non-Small Cell Lung Cancer Subtypes Using Computed Tomography Perfusion

Molecular Pathology in Oncology Target and Drug Discovery

Contact Info

Product

Resources

About