Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice | springermedizin.de

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Investigational New Drugs

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05.01.2019 | PRECLINICAL STUDIES

Biodistribution, pharmacokinetics and radioimmunotherapy of ¹⁸⁸Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice

verfasst von: Ya-Jen Chang, Chung-Li Ho, Kai-Hung Cheng, Wan-I Kuo, Wan-Chi Lee, Keng-Li Lan, Chih-Hsien Chang

Erschienen in: Investigational New Drugs | Ausgabe 5/2019

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Summary

Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear ¹⁸⁸Re achieved better therapeutic effect on lung cancer. Methods¹⁸⁸Re-cetuximab administered by the i.v. route in human NCI-H292 lung tumor-bearing mice was investigated. NanoSPECT/CT images were taken to evaluate the distribution and tumor targeting of ¹⁸⁸Re-cetuximab in mice. The anti-tumor effect of ¹⁸⁸Re-cetuximab was assessed by the tumor growth inhibition, survival ratio. Results For nanoSPECT/CT imaging, a significant uptake in tumor was observed at 24 and 48 h following the injection of ¹⁸⁸Re-cetuximab. The anti-tumor effect of ¹⁸⁸Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with ¹⁸⁸Re-cetuximab showed a better mean tumor growth inhibition rate (MGI = 0.049) and longer median survival time and lifespan (62.50 d; 70.07%) than those treated with ¹⁸⁸Re-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for ¹⁸⁸Re-cetuximab (CI = 6.135 and 9.276). Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of ¹⁸⁸Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from ¹⁸⁸Re-cetuximab for diagnosis and therapy of oncology applications in the future.

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1.

Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83(5):584–594. https://doi.org/10.4065/83.5.584 CrossRefPubMed

2.

Privitera G, Luca T, Musso N, Vancheri C, Crimi N, Barresi V, Condorelli D, Castorina S (2016) In vitro antiproliferative effect of trastuzumab (Herceptin((R))) combined with cetuximab (Erbitux((R))) in a model of human non-small cell lung cancer expressing EGFR and HER2. Clin Exp Med 16(2):161–168. https://doi.org/10.1007/s10238-015-0343-8 CrossRefPubMed

3.

Patil N, Abba M, Allgayer H (2012) Cetuximab and biomarkers in non-small-cell lung carcinoma. Biologics 6:221–231. https://doi.org/10.2147/BTT.S24217 CrossRefPubMedPubMedCentral

4.

Pujol JL, Pirker R, Lynch TJ, Butts CA, Rosell R, Shepherd FA, Vansteenkiste J, O'Byrne KJ, de Blas B, Heighway J, von Heydebreck A, Thatcher N (2014) Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer. Lung Cancer 83(2):211–218. https://doi.org/10.1016/j.lungcan.2013.11.006 CrossRefPubMed

5.

Kim SM, Kim JS, Kim JH, Yun CO, Kim EM, Kim HK, Solca F, Choi SY, Cho BC (2010) Acquired resistance to cetuximab is mediated by increased PTEN instability and leads cross-resistance to gefitinib in HCC827 NSCLC cells. Cancer Lett 296(2):150–159. https://doi.org/10.1016/j.canlet.2010.04.006 CrossRefPubMed

6.

Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U, Team FS (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373(9674):1525–1531. https://doi.org/10.1016/S0140-6736(09)60569-9 CrossRefPubMed

7.

Rosell R, Robinet G, Szczesna A, Ramlau R, Constenla M, Mennecier BC, Pfeifer W, O'Byrne KJ, Welte T, Kolb R, Pirker R, Chemaissani A, Perol M, Ranson MR, Ellis PA, Pilz K, Reck M (2008) Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Annals of oncology : official journal of the European Society for. Med Oncol 19(2):362–369. https://doi.org/10.1093/annonc/mdm474 CrossRef

8.

Gatzemeier U, von Pawel J, Vynnychenko I, Zatloukal P, de Marinis F, Eberhardt WE, Paz-Ares L, Schumacher KM, Goddemeier T, O'Byrne KJ, Pirker R (2011) First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX phase 3 study. Lancet Oncol 12(1):30–37. https://doi.org/10.1016/S1470-2045(10)70278-3 CrossRefPubMed

9.

Milenic DE, Brady ED, Brechbiel MW (2004) Antibody-targeted radiation cancer therapy. Nat Rev Drug Discov 3(6):488–499. https://doi.org/10.1038/nrd1413 CrossRefPubMed

10.

Ting G, Chang CH, Wang HE, Lee TW (2010) Nanotargeted radionuclides for cancer nuclear imaging and internal radiotherapy. J Biomed Biotechnol 2010:1–17. https://doi.org/10.1155/2010/953537 CrossRef

11.

Davis TA, Kaminski MS, Leonard JP, Hsu FJ, Wilkinson M, Zelenetz A, Wahl RL, Kroll S, Coleman M, Goris M, Levy R, Knox SJ (2004) The radioisotope contributes significantly to the activity of radioimmunotherapy. Clin Cancer Res 10(23):7792–7798. https://doi.org/10.1158/1078-0432.CCR-04-0756

12.

Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, Multani P, White CA (2002) Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol 20(10):2453–2463. https://doi.org/10.1200/JCO.2002.11.076

13.

Gordon LI, Witzig T, Molina A, Czuczman M, Emmanouilides C, Joyce R, Vo K, Theuer C, Pohlman B, Bartlett N, Wiseman G, Darif M, White C (2004) Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma. Clin Lymphoma 5(2):98–101CrossRefPubMed

14.

Bonner JA (2016) Cetuximab or cisplatin as a radiosensitizer in locoregionally advanced head and neck cancer: recent results. Transl Cancer Res 5(3):234–237. https://doi.org/10.21037/tcr.2016.06.22

15.

Bianco C, Tortora G, Bianco R, Caputo R, Veneziani BM, Caputo R, Damiano V, Troiani T, Fontanini G, Raben D, Pepe S, Bianco AR, Ciardiello F (2002) Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res 8(10):3250–3258

16.

Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, Chinnaiyan AM, Harari PM (2005) Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res 65(8):3328–3335. https://doi.org/10.1158/0008-5472.CAN-04-3547 CrossRefPubMed

17.

Raben D, Helfrich B, Chan DC, Ciardiello F, Zhao L, Franklin W, Baron AE, Zeng C, Johnson TK, Bunn PA Jr (2005) The effects of cetuximab alone and in combination with radiation and/or chemotherapy in lung cancer. Clin Cancer Res 11(2 Pt 1):795–805

18.

Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, Mendelsohn J, Fan Z (2000) In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res 6(2):701–708

19.

Huang SM, Bock JM, Harari PM (1999) Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 59(8):1935–1940PubMed

20.

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–578. https://doi.org/10.1056/NEJMoa053422 CrossRefPubMed

21.

Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11(1):21–28. https://doi.org/10.1016/S1470-2045(09)70311-0 CrossRefPubMed

22.

Stabin MG, Siegel JA (2003) Physical models and dose factors for use in internal dose assessment. Health Phys 85(3):294–310CrossRefPubMed

23.

Molina-Trinidad EM, de Murphy CA, Ferro-Flores G, Murphy-Stack E, Jung-Cook H (2006) Radiopharmacokinetic and dosimetric parameters of ¹⁸⁸Re-lanreotide in athymic mice with induced human cancer tumors. Int J Pharm 310(1–2):125–130. https://doi.org/10.1016/j.ijpharm.2005.11.043 CrossRefPubMed

24.

Lin YY, Chang CH, Li JJ, Stabin MG, Chang YJ, Chen LC, Lin MH, Tseng YL, Lin WJ, Lee TW, Ting G, Chang CA, Chen FD, Wang HE (2011) Pharmacokinetics and dosimetry of ¹¹¹In/¹⁸⁸Re-labeled PEGylated liposomal drugs in two colon carcinoma-bearing mouse models. Cancer Biother Radiopharm 26(3):373–380. https://doi.org/10.1089/cbr.2010.0906 CrossRefPubMedPubMedCentral

25.

Chang CH, Stabin MG, Chang YJ, Chen LC, Chen MH, Chang TJ, Lee TW, Ting G (2008) Comparative dosimetric evaluation of nanotargeted ¹⁸⁸Re-(DXR)-liposome for internal radiotherapy. Cancer Biother Radiopharm 23(6):749–758. https://doi.org/10.1089/cbr.2008.0489 CrossRefPubMed

26.

Bentel GCNC, Noell KT (1989) Treatment planning and dose calculation in radiation oncology. Pergamon Press, Oxford

27.

O'Donoghue JA, Baidoo N, Deland D, Welt S, Divgi CR, Sgouros G (2002) Hematologic toxicity in radioimmunotherapy: dose-response relationships for I-131 labeled antibody therapy. Cancer Biother Radiopharm 17(4):435–443CrossRefPubMed

28.

Cao S, Rustum YM (2000) Synergistic antitumor activity of irinotecan in combination with 5-fluorouracil in rats bearing advanced colorectal cancer: role of drug sequence and dose. Cancer Res 60(14):3717–3721PubMed

29.

Reilly RM, Chen P, Wang J, Scollard D, Cameron R, Vallis KA (2006) Preclinical pharmacokinetic, biodistribution, toxicology, and dosimetry studies of ¹¹¹In-DTPA-human epidermal growth factor: an auger electron-emitting radiotherapeutic agent for epidermal growth factor receptor-positive breast cancer. J Nucl Med 47(6):1023–1031

30.

Morgillo F, Kim WY, Kim ES, Ciardiello F, Hong WK, Lee HY (2007) Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res 13(9):2795–2803. https://doi.org/10.1158/1078-0432.CCR-06-2077

31.

Maddalena ME, Fox J, Chen J, Feng W, Cagnolini A, Linder KE, Tweedle MF, Nunn AD, Lantry LE (2009) ¹⁷⁷Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med 50(12):2017–2024

32.

Goetz M, Hoetker MS, Diken M, Galle PR, Kiesslich R (2013) In vivo molecular imaging with cetuximab, an anti-EGFR antibody, for prediction of response in xenograft models of human colorectal cancer. Endoscopy 45(6):469–477. https://doi.org/10.1055/s-0032-1326361 CrossRefPubMed

33.

van Dijk LK, Hoeben BA, Kaanders JH, Franssen GM, Boerman OC, Bussink J (2013) Imaging of epidermal growth factor receptor expression in head and neck cancer with SPECT/CT and ¹¹¹In-labeled cetuximab-F(ab')2. J Nucl Med 54(12):2118–2124. https://doi.org/10.2967/jnumed.113.123612

34.

Shih YH, Peng CL, Lee SY, Chiang PF, Yao CJ, Lin WJ, Luo TY, Shieh MJ (2015) ¹¹¹In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma. Oncotarget 6(18):16601–16610. https://doi.org/10.18632/oncotarget.3968 CrossRefPubMedPubMedCentral

35.

Hoeben BA, Molkenboer-Kuenen JD, Oyen WJ, Peeters WJ, Kaanders JH, Bussink J, Boerman OC (2011) Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model. Int J Cancer 129(4):870–878. https://doi.org/10.1002/ijc.25727 CrossRefPubMed

36.

Shih BB, Chang YF, Cheng CC, Yang HJ, Chang KW, Ho AS, Lin HC, Yeh C, Chang CC (2017) SPECT imaging evaluation of ¹¹¹indium-chelated cetuximab for diagnosing EGFR-positive tumor in an HCT-15-induced colorectal xenograft. J Chin Med Assoc 80(12):766–773. https://doi.org/10.1016/j.jcma.2017.02.010

37.

Makris NE, Boellaard R, van Lingen A, Lammertsma AA, van Dongen GA, Verheul HM, Menke CW, Huisman MC (2015) PET/CT-derived whole-body and bone marrow dosimetry of ⁸⁹Zr-cetuximab. J Nucl Med 56(2):249–254. https://doi.org/10.2967/jnumed.114.147819

38.

Perk LR, Visser GW, Vosjan MJ, Stigter-van Walsum M, Tijink BM, Leemans CR, van Dongen GA (2005) ⁸⁹Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals ⁹⁰Y and ¹⁷⁷Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med 46(11):1898–1906

39.

van Dijk LK, Yim CB, Franssen GM, Kaanders JH, Rajander J, Solin O, Gronroos TJ, Boerman OC, Bussink J (2016) PET of EGFR with ⁶⁴Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts. Contrast Media Mol Imaging 11(1):65–70. https://doi.org/10.1002/cmmi.1659

40.

Guo Y, Parry JJ, Laforest R, Rogers BE, Anderson CJ (2013) The role of p53 in combination radioimmunotherapy with ⁶⁴Cu-DOTA-cetuximab and cisplatin in a mouse model of colorectal cancer. J Nucl Med 54(9):1621–1629. https://doi.org/10.2967/jnumed.112.118539

41.

Schechter NR, Wendt RE 3rd, Yang DJ, Azhdarinia A, Erwin WD, Stachowiak AM, Broemeling LD, Kim EE, Cox JD, Podoloff DA, Ang KK (2004) Radiation dosimetry of ^99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck. J Nucl Med 45(10):1683–1687

42.

Chakravarty R, Chakraborty S, Sarma HD, Nair KV, Rajeswari A, Dash A (2016) ⁹⁰Y/¹⁷⁷Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation. J Label Compd Radiopharm 59(9):354–363. https://doi.org/10.1002/jlcr.3413 CrossRef

43.

Song IH, Lee TS, Park YS, Lee JS, Lee BC, Moon BS, An GI, Lee HW, Kim KI, Lee YJ, Kang JH, Lim SM (2016) Immuno-PET imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-labeled anti-EGFR antibody in esophageal squamous cell carcinoma model. J Nucl Med 57(7):1105–1111. https://doi.org/10.2967/jnumed.115.167155

44.

Iznaga-Escobar N (1998) ¹⁸⁸Re-direct labeling of monoclonal antibodies for radioimmunotherapy of solid tumors: biodistribution, normal organ dosimetry, and toxicology. Nucl Med Biol 25(5):441–447CrossRefPubMed

45.

O'Donoghue JA, Bardies M, Wheldon TE (1995) Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 36(10):1902–1909

46.

Wang HY, Lin WY, Chen MC, Lin T, Chao CH, Hsu FN, Lin E, Huang CY, Luo TY, Lin H (2013) Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma. Int J Radiat Biol 89(5):346–355. https://doi.org/10.3109/09553002.2013.762136 CrossRefPubMed

47.

Li G, Wang Y, Huang K, Zhang H, Peng W, Zhang C (2005) The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of ¹⁸⁸Re-herceptin. Nucl Med Biol 32(1):59–65. https://doi.org/10.1016/j.nucmedbio.2004.09.003 CrossRefPubMed

48.

Dittmann K, Mayer C, Fehrenbacher B, Schaller M, Raju U, Milas L, Chen DJ, Kehlbach R, Rodemann HP (2005) Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem 280(35):31182–31189. https://doi.org/10.1074/jbc.M506591200 CrossRefPubMed

49.

Dittmann K, Mayer C, Fehrenbacher B, Schaller M, Kehlbach R, Rodemann HP (2011) Nuclear epidermal growth factor receptor modulates cellular radio-sensitivity by regulation of chromatin access. Radiother Oncol 99(3):317–322. https://doi.org/10.1016/j.radonc.2011.06.001

50.

Morgan MA, Parsels LA, Kollar LE, Normolle DP, Maybaum J, Lawrence TS (2008) The combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation in pancreatic cancer. Clin Cancer Res 14(16):5142–5149. https://doi.org/10.1158/1078-0432.CCR-07-4072

51.

Kimple RJ, Vaseva AV, Cox AD, Baerman KM, Calvo BF, Tepper JE, Shields JM, Sartor CI (2010) Radiosensitization of epidermal growth factor receptor/HER2-positive pancreatic cancer is mediated by inhibition of Akt independent of ras mutational status. Clin Cancer Res 16(3):912–923. https://doi.org/10.1158/1078-0432.CCR-09-1324

52.

Rembielak AI, Jain P, Jackson AS, Green MM, Santorelli GR, Whitfield GA, Crellin A, Garcia-Alonso A, Radhakrishna G, Cullen J, Taylor MB, Swindell R, West CM, Valle J, Saleem A, Price PM (2014) Phase II trial of Cetuximab and conformal radiotherapy only in locally advanced pancreatic Cancer with concurrent tissue sampling feasibility study. Transl Oncol 7(1):55–64CrossRefPubMedPubMedCentral

53.

Bonner JA, Trummell HQ, Bonner AB, Willey CD, Bredel M, Yang ES (2015) Enhancement of Cetuximab-induced Radiosensitization by JAK-1 inhibition. BMC Cancer 15:673. https://doi.org/10.1186/s12885-015-1679-x CrossRefPubMedPubMedCentral

Titel: Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice
verfasst von: Ya-Jen Chang
Chung-Li Ho
Kai-Hung Cheng
Wan-I Kuo
Wan-Chi Lee
Keng-Li Lan
Chih-Hsien Chang
Publikationsdatum: 05.01.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 5/2019
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-018-00718-8

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