Open Access

Integrin αVβ3‑targeted SPECT/CT for the assessment of Bevacizumab therapy in orthotopic lung cancer xenografts

  • Authors:
    • Bin Chen
    • Wenqi Zhang
    • Bin Ji
    • Qingjie Ma
    • Dandan Li
    • Shi Gao
  • View Affiliations

  • Published online on: January 29, 2018     https://doi.org/10.3892/ol.2018.7901
  • Pages: 4201-4206
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

The present study aimed to determine the utility of 99mTc-3PRGD2 single photon emission computed tomography (SPECT)/computed tomography (CT) for the non‑invasive monitoring of the response of integrin αvβ3 expression to anti‑angiogenic treatment with bevacizumab. Bevacizumab or vehicle therapy was performed in athymic nu/nu mice bearing A549 lung tumors (moderately high integrin αvβ3 expression) or PC‑3 prostate tumors (low integrin αvβ3 expression) at a dose of 1 mg twice a week. The average tumor volume was 180±90 mm3 the day prior to baseline SPECT/CT. Longitudinal 99mTc‑3PRGD2 SPECT/CT imaging was performed at baseline (‑1 day) and at days 5 and 15. Tumors were harvested at all imaging time points for histopathological analysis with hematoxylin and eosin (H&E) and immunohistochemistry staining. Results revealed a significant difference in tumor volume between vehicle‑ and bevacizumab‑treated groups at 5 and 15 days following the start of treatment in the A549 lung model (P<0.05). At 5 days after the start of therapy, the percent injected dose per gram of tissue (%ID/g) and tumor‑to‑muscle ratio for bevacizumab‑treated A549 declined persistently (P<0.05). However, for the vehicle‑treated A549 model, the %ID and %ID/g value increased 5 days after the start of treatment (P<0.05). For the PC‑3 model, slow‑growing tumors and low tumor uptake was observed throughout the study. Alterations in tumor vasculature were confirmed by histopathological H&E analysis and immunohistochemistry. In conclusion, longitudinal imaging using 99mTc‑3PRGD2 SPECT/CT may be a useful tool for monitoring the anti‑angiogenic effect of bevacizumab therapy.

References

1 

Rayson D, Vantyghem SA and Chambers AF: Angiogenesis as a target for breast cancer therapy. J Mammary Gland Biol Neoplasia. 4:415–423. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Ferrara N and Kerbel RS: Angiogenesis as a therapeutic target. Nature. 438:967–974. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Rodgers M, Soares M, Epstein D, Yang H, Fox D and Eastwood A: Bevacizumab in combination with a taxane for the first-line treatment of her2-negative metastatic breast cancer. Health Technol Assess. 15 Suppl 1:S1–S12. 2011. View Article : Google Scholar

4 

Sheng J, Yang YP, Yang BJ, Zhao YY, Ma YX, Hong SD, Zhang YX, Zhao HY, Huang Y and Zhang L: Efficacy of addition of antiangiogenic agents to taxanes-containing chemotherapy in advanced nonsmall-cell lung cancer: A meta-analysis and systemic review. Medicine (Baltimore). 94:e12822015. View Article : Google Scholar : PubMed/NCBI

5 

Lee SM, BAAS P and Wakelee H: Anti-angiogenesis drugs in lung cancer. Respirology. 15:387–392. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Lange A, Prenzler A, Frank M, Golpon H, Welte T and von der Schulenburg JM: A systematic review of the cost-effectiveness of targeted therapies for metastatic non-small cell lung cancer (nsclc). BMC Pulm Med. 14:1922014. View Article : Google Scholar : PubMed/NCBI

7 

Schreuder SM, Lensing R, Stoker J and Bipat S: Monitoring treatment response in patients undergoing chemoradiotherapy for locally advanced uterine cervical cancer by additional diffusion-weighted imaging: A systematic review. J Magn Reson Imaging. 42:572–594. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Lei L, Wang X and Chen Z: PET/CT imaging for monitoring recurrence and evaluating response to treatment in breast cancer. Adv Clin Exp Med. 25:377–382. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Ji B, Chen B, Wang T, Song Y, Chen M, Ji T, Wang X, Gao S and Ma Q: 99mTc-3PRGD2 SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer. Eur J Nucl Med Mol Imaging. 42:1362–1370. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Ma Q, Min K, Wang T, Chen B, Wen Q, Wang F, Ji T and Gao S: (99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab. Ann Nucl Med. 29:519–527. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Jia B, Liu Z, Zhu Z, Shi J, Jin X, Zhao H, Li F, Liu S and Wang F: Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin αvβ3-selective radiotracer 99mTc-3PRGD2 in non-human primates. Mol Imaging Biol. 13:730–736. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Niu G and Chen X: Why integrin as a primary target for imaging and therapy. Theranostics. 1:30–47. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Wang L, Shi J, Kim YS, Zhai S, Jia B, Zhao H, Liu Z, Wang F, Chen X and Liu S: Improving tumor-targeting capability and pharmacokinetics of (99m)Tc-labeled cyclic RGD dimers with PEG(4) linkers. Mol Pharm. 6:231–245. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Zhou Y, Kim YS, Chakraborty S, Shi J, Gao H and Liu S: 99mTc-labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin αvβ3 expression. Mol Imaging. 10:386–397. 2011.PubMed/NCBI

15 

Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S and Distler O: Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 47:149–161. 2003.PubMed/NCBI

16 

Wong CI, Koh TS, Soo R, Hartono S, Thng CH, McKeegan E, Yong WP, Chen CS, Lee SC, Wong J, et al: Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. J Clin Oncol. 27:4718–4726. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Jiang F, Albert DH, Luo Y, Tapang P, Zhang K, Davidsen SK, Fox GB, Lesniewski R and McKeegan EM: ABT-869, a multitargeted receptor tyrosine kinase inhibitor, reduces tumor microvascularity and improves vascular wall integrity in preclinical tumor models. J Pharmacol Exp Ther. 338:134–142. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Tannir NM, Wong YN, Kollmannsberger CK, Ernstoff MS, Perry DJ, Appleman LJ, Posadas EM, Cho D, Choueiri TK, Coates A, et al: Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. Eur J Cancer. 47:2706–2714. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Gullino PM: Angiogenesis and neoplasia. N Engl J Med. 305:884–885. 1981. View Article : Google Scholar : PubMed/NCBI

20 

Koukourakis MI, Giatromanolaki A, Sivridis E and Fezoulidis I: Cancer vascularization: Implications in radiotherapy? Int J Radiat Oncol Biol Phys. 48:545–553. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Morrison MS, Ricketts SA, Barnett J, Cuthbertson A, Tessier J and Wedge SR: Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy. J Nucl Med. 50:116–122. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Battle MR, Goggi JL, Allen L, Barnett J and Morrison MS: Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled αVbeta3-integrin and αVbeta5-integrin imaging agent. J Nucl Med. 52:424–430. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Sun X, Yan Y, Liu S, Cao Q, Yang M, Neamati N, Shen B, Niu G and Chen X: 18F-FPPRGD2 and 18F-FDG PET of response to Abraxane therapy. J Nucl Med. 52:140–146. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Zhou Y, Kim YS, Lu X and Liu S: Evaluation of 99mTc-labeled cyclic RGD dimers: Impact of cyclic RGD peptides and 99mTc chelates on biological properties. Bioconjug Chem. 23:586–595. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Chen, B., Zhang, W., Ji, B., Ma, Q., Li, D., & Gao, . (2018). Integrin αVβ3‑targeted SPECT/CT for the assessment of Bevacizumab therapy in orthotopic lung cancer xenografts. Oncology Letters, 15, 4201-4206. https://doi.org/10.3892/ol.2018.7901
MLA
Chen, B., Zhang, W., Ji, B., Ma, Q., Li, D., Gao, ."Integrin αVβ3‑targeted SPECT/CT for the assessment of Bevacizumab therapy in orthotopic lung cancer xenografts". Oncology Letters 15.4 (2018): 4201-4206.
Chicago
Chen, B., Zhang, W., Ji, B., Ma, Q., Li, D., Gao, ."Integrin αVβ3‑targeted SPECT/CT for the assessment of Bevacizumab therapy in orthotopic lung cancer xenografts". Oncology Letters 15, no. 4 (2018): 4201-4206. https://doi.org/10.3892/ol.2018.7901