ArticleEuropean journal of nuclear medicine and molecular imaging2011
PET imaging of early response to the tyrosine kinase inhibitor ZD4190.
Article in European journal of nuclear medicine and molecular imaging, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
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- N-Succinimidyl 4-[(18)F]-fluoromethylbenzoate-labeled dimeric RGD peptide for imaging tumor integrin expression.Amino acids · 2012Article
- PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2.European journal of nuclear medicine and molecular imaging · 2012Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeWe evaluated noninvasive positron emission tomography (PET) imaging for monitoring tumor response to the VEGFR-2 tyrosine kinase (TK) inhibitor ZD4190 during cancer therapy. EXPERIMENTAL
designOrthotopic MDA-MB-435 tumor-bearing mice were treated with ZD4190 (100 mg/kg orally per day for three consecutive days). Tumor growth was monitored by caliper measurement. During the therapeutic period, longitudinal PET scans were acquired using (18)F-FDG, (18)F-FLT and (18)F-FPPRGD2 as imaging tracers to evaluate tumor glucose metabolism, tumor cell proliferation, and angiogenesis, respectively. Imaging metrics were validated by immunohistochemical analysis of Ki67, GLUT-1, F4/80, CD31, murine integrin β3, and human integrin αvβ3.
resultsThree consecutive daily oral administrations of 100 mg/kg of ZD4190 were effective in delaying MDA-MB-435 tumor growth. A significant difference in tumor volume was observed on day 7 between the treatment group and the control group (p < 0.01). After the final treatment, tumor growth resumed after a short delay. In the control tumors, (18)F-FPPRGD2 uptake was stable between days 0 and 7. In ZD4190-treated tumors, (18)F-FPPRGD2 uptake had decreased significantly relative to baseline by 26.74 ± 8.12% (p < 0.05) on day 1 and by 41.19 ± 6.63% (p < 0.01) on day 3, then had returned to baseline on day 7. Tumor uptake of (18)F-FLT had also decreased on both day 1 and day 3 after initiation of ZD4190 treatment. No significant change in (18)F-FDG uptake in ZD4190-treated tumors was observed, however, compared with the control group. All of the imaging findings were supported by ex vivo analysis of related biomarkers.
conclusionThe longitudinal imaging results demonstrated the usefulness of quantitative (18)F-FLT and (18)F-FPPRGD2 PET imaging in evaluating the early antiproliferative and antiangiogenic effects of ZD4190. The quantification data from the PET imaging were consistent with the pattern of initial growth inhibition with treatment, followed by tumor relapse after treatment cessation.
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