Bioluminescence Imaging of Therapy Response Does Not Correlate with FDG-PET Response in a Mouse Model of Burkitt Lymphoma

Overview

Journal Am J Nucl Med Mol Imaging

Date 2012 Nov 8

PMID 23133822

Citations 3

Authors

Marijke De Saint-Hubert

Ellen Devos

Abdelilah Ibrahimi

Zeger Debyser

Luc Mortelmans

Felix M Mottaghy

Affiliations

Soon will be listed here.

Abstract

Since the development and evaluation of novel anti-cancer therapies require molecular insight in the disease state, both FDG-PET and BLI imaging were evaluated in a Burkitt B-cell lymphoma xenograft model treated with cyclophosphamide or temsirolimus. Daudi xenograft mice were treated with either cyclophosphamide or temsirolimus and imaged with BLI and FDG-PET on d0 (before treatment), d2, d4, d7, d9 and d14 following the start of therapy. Besides tumor volume changes, therapy response was assessed with immunohistochemical analysis (apoptosis). BLI revealed a flare following both therapeutics that was significantly higher when compared to control tumors. FDG-PET decreased immediatelly, long before the tumor reduced in size. Late after therapy, BLI signal intensities decreased significantly compared to baseline subsequent to tumor size reduction while apoptosis was immediately induced following both treatment regimen. Unlike FDG, BLI was not able to reflect reduced levels of viable cells and was not able to predict tumor size response and apoptosis response.

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References

Mandl S, Mari C, Edinger M, Negrin R, Tait J, Contag C . Multi-modality imaging identifies key times for annexin V imaging as an early predictor of therapeutic outcome. Mol Imaging. 2004; 3(1):1-8. DOI: 10.1162/15353500200403157. View

Keyaerts M, Heneweer C, Gainkam L, Caveliers V, Beattie B, Martens G . Plasma protein binding of luciferase substrates influences sensitivity and accuracy of bioluminescence imaging. Mol Imaging Biol. 2010; 13(1):59-66. DOI: 10.1007/s11307-010-0325-x. View

Branchini B, Magyar R, Murtiashaw M, Anderson S, Helgerson L, Zimmer M . Site-directed mutagenesis of firefly luciferase active site amino acids: a proposed model for bioluminescence color. Biochemistry. 1999; 38(40):13223-30. DOI: 10.1021/bi991181o. View

Ibrahimi A, Velde G, Reumers V, Toelen J, Thiry I, Vandeputte C . Highly efficient multicistronic lentiviral vectors with peptide 2A sequences. Hum Gene Ther. 2009; 20(8):845-60. DOI: 10.1089/hum.2008.188. View

Morris M, Akhurst T, Larson S, Ditullio M, Chu E, Siedlecki K . Fluorodeoxyglucose positron emission tomography as an outcome measure for castrate metastatic prostate cancer treated with antimicrotubule chemotherapy. Clin Cancer Res. 2005; 11(9):3210-6. PMC: 2040333. DOI: 10.1158/1078-0432.CCR-04-2034. View

Quon A, Gambhir S . FDG-PET and beyond: molecular breast cancer imaging. J Clin Oncol. 2005; 23(8):1664-73. DOI: 10.1200/JCO.2005.11.024. View

Svensson R, Barnes J, Rokhlin O, Cohen M, Henry M . Chemotherapeutic agents up-regulate the cytomegalovirus promoter: implications for bioluminescence imaging of tumor response to therapy. Cancer Res. 2007; 67(21):10445-54. DOI: 10.1158/0008-5472.CAN-07-1955. View

Lembert N . Firefly luciferase can use L-luciferin to produce light. Biochem J. 1996; 317 ( Pt 1):273-7. PMC: 1217473. DOI: 10.1042/bj3170273. View

Hingorani M, White C, Zaidi S, Merron A, Peerlinck I, Gore M . Radiation-mediated up-regulation of gene expression from replication-defective adenoviral vectors: implications for sodium iodide symporter gene therapy. Clin Cancer Res. 2008; 14(15):4915-24. DOI: 10.1158/1078-0432.CCR-07-4049. View

10.

Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T . Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med. 1992; 33(11):1972-80. View

11.

Brepoels L, De Saint-Hubert M, Stroobants S, Verhoef G, Balzarini J, Mortelmans L . Dose-response relationship in cyclophosphamide-treated B-cell lymphoma xenografts monitored with [18F]FDG PET. Eur J Nucl Med Mol Imaging. 2010; 37(9):1688-95. DOI: 10.1007/s00259-010-1479-0. View

12.

Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Maertens J, Bormans G . Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood. 2003; 102(1):53-9. DOI: 10.1182/blood-2002-12-3842. View

13.

Blasberg R . In vivo molecular-genetic imaging: multi-modality nuclear and optical combinations. Nucl Med Biol. 2003; 30(8):879-88. DOI: 10.1016/s0969-8051(03)00115-x. View

14.

Deroose C, Reumers V, Gijsbers R, Bormans G, Debyser Z, Mortelmans L . Noninvasive monitoring of long-term lentiviral vector-mediated gene expression in rodent brain with bioluminescence imaging. Mol Ther. 2006; 14(3):423-31. DOI: 10.1016/j.ymthe.2006.05.007. View

15.

De Saint-Hubert M, Brepoels L, Devos E, Vermaelen P, Groot T, Tousseyn T . Molecular imaging of therapy response with (18)F-FLT and (18)F-FDG following cyclophosphamide and mTOR inhibition. Am J Nucl Med Mol Imaging. 2012; 2(1):110-21. PMC: 3478112. View

16.

Lembert N, Idahl L . Regulatory effects of ATP and luciferin on firefly luciferase activity. Biochem J. 1995; 305 ( Pt 3):929-33. PMC: 1136347. DOI: 10.1042/bj3050929. View

17.

SCHWIMMER J, Essner R, Patel A, Jahan S, Shepherd J, Park K . A review of the literature for whole-body FDG PET in the management of patients with melanoma. Q J Nucl Med. 2000; 44(2):153-67. View

18.

Krak N, Boellaard R, Hoekstra O, Twisk J, Hoekstra C, Lammertsma A . Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging. 2005; 32(3):294-301. DOI: 10.1007/s00259-004-1566-1. View

19.

Brepoels L, Stroobants S, Vandenberghe P, Spaepen K, Dupont P, Nuyts J . Effect of corticosteroids on 18F-FDG uptake in tumor lesions after chemotherapy. J Nucl Med. 2007; 48(3):390-7. View

20.

Kim K, Kang J, Chung J, Lee Y, Jeong J, Lee D . Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells. J Nucl Med. 2007; 48(9):1553-61. DOI: 10.2967/jnumed.106.038612. View