Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft | springermedizin.de

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Breast Cancer Research and Treatment

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01.11.2011 | Preclinical study

Post-lumpectomy intracavitary retention and lymph node targeting of ^99mTc-encapsulated liposomes in nude rats with breast cancer xenograft

verfasst von: Shihong Li, Beth Goins, William T. Phillips, Marcela Saenz, Pamela M. Otto, Ande Bao

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2011

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Abstract

Liposomes are recognized drug delivery systems with tumor-targeting capability. In addition, therapeutic or diagnostic radionuclides can be efficiently loaded into liposomes. This study investigated the feasibility of utilizing radiotherapeutic liposomes as a new post-lumpectomy radiotherapy for early-stage breast cancer by determining the locoregional retention and systemic distribution of liposomes radiolabeled with technetium-99m (^99mTc) in an orthotopic MDA-MB-231 breast cancer xenograft nude rat model. To test this new brachytherapy approach, a positive surgical margin lumpectomy model was set up by surgically removing the xenograft and deliberately leaving a small tumor remnant in the surgical cavity. Neutral, anionic, and cationic surface-charged fluorescent liposomes of 100 and 400 nm diameter were manufactured and labeled with ^99mTc-BMEDA. Locoregional retention and systemic distribution of ^99mTc-liposomes injected into the post-lumpectomy cavity were determined using non-invasive nuclear imaging, ex vivo tissue gamma counting and fluorescent stereomicroscopic imaging. The results indicated that ^99mTc-liposomes were effectively retained in the surgical cavity (average retention was 55.7 ± 24.2% of injected dose for all rats at 44 h post-injection) and also accumulated in the tumor remnant (66.9 ± 100.4%/g for all rats). The majority of cleared ^99mTc was metabolized quickly and excreted into feces and urine, exerting low radiation burden on vital organs. In certain animals ^99mTc-liposomes significantly accumulated in the peripheral lymph nodes, especially 100 nm liposomes with anionic surface charge. The results suggest that post-lumpectomy intracavitary administration of therapeutic radionuclides delivered by 100-nm anionic liposome carrier is a potential therapy for the simultaneous treatment of the surgical cavity and the draining lymph nodes of early-stage breast cancer.

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1.

Early Breast Cancer Trialists’ Collaborative Group (1995) Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. N Engl J Med 333:1444–1455CrossRef

2.

Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD (1996) Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial Scottish Cancer Trials Breast Group. Lancet 348:708–713. doi:10.1016/S0140-6736(96)02133-2 PubMedCrossRef

3.

Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabar L, Nordgren H, Adami HO (1999) 10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 17:2326–2333PubMed

4.

Van de Steene J, Vinh-Hung V, Cutuli B, Storme G (2004) Adjuvant radiotherapy for breast cancer: effects of longer follow-up. Radiother Oncol 72:35–43. doi:10.1016/j.radonc.2004.04.004 PubMedCrossRef

5.

Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, Salvadori B, Zucali R (2001) Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 12:997–1003PubMedCrossRef

6.

Polgar C, Strnad V, Major T (2005) Brachytherapy for partial breast irradiation: the European experience. Semin Radiat Oncol 15:116–122. doi:10.1016/j.semradonc.2004.10.004 PubMedCrossRef

7.

Vicini FA, Arthur DW (2005) Breast brachytherapy: North American experience. Semin Radiat Oncol 15:108–115. doi:10.1016/j.semradonc.2004.10.005 PubMedCrossRef

8.

Arthur D (2003) Accelerated partial breast irradiation: a change in treatment paradigm for early stage breast cancer. J Surg Oncol 84:185–191. doi:10.1002/jso.10318 PubMedCrossRef

9.

Dirbas FM (2009) Accelerated partial breast irradiation: where do we stand? J Natl Compr Cancer Netw 7:215–225

10.

Vaidya JS, Tobias JS, Baum M, Wenz F, Kraus-Tiefenbacher U, D’souza D, Keshtgar M, Massarut S, Hilaris B, Saunders C, Joseph D (2005) TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation. Semin Radiat Oncol 15:84–91. doi:10.1016/j.semradonc.2004.10.007 PubMedCrossRef

11.

Veronesi U, Orecchia R, Luini A, Galimberti V, Gatti G, Intra M, Veronesi P, Leonardi MC, Ciocca M, Lazzari R, Caldarella P, Simsek S, Silva LS, Sances D (2005) Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery: experience with 590 cases. Ann Surg 242:101–106. doi:10.1097/01.sla.0000167927.82353.bc PubMedCrossRef

12.

Vicini FA, Baglan KL, Kestin LL, Mitchell C, Chen PY, Frazier RC, Edmundson G, Goldstein NS, Benitez P, Huang RR, Martinez A (2001) Accelerated treatment of breast cancer. J Clin Oncol 19:1993–2001PubMed

13.

Arthur DW, Vicini FA, Kuske RR, Wazer DE, Nag S (2003) Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy 2:124–130. doi:10.1016/S1538-4721(03)00107-7 PubMedCrossRef

14.

Baglan KL, Sharpe MB, Jaffray D, Frazier RC, Fayad J, Kestin LL, Remouchamps V, Martinez AA, Wong J, Vicini FA (2003) Accelerated partial breast irradiation using 3D conformal radiation therapy (3D-CRT). Int J Radiat Oncol Biol Phys 55:302–311. doi:10.1016/S0360-3016(02)03811-7 PubMedCrossRef

15.

Weed DW, Edmundson GK, Vicini FA, Chen PY, Martinez AA (2005) Accelerated partial breast irradiation: a dosimetric comparison of three different techniques. Brachytherapy 4:121–129. doi:10.1016/j.brachy.2004.12.005 PubMedCrossRef

16.

Vaidya JS, Baum M, Tobias JS, D’Souza DP, Naidu SV, Morgan S, Metaxas M, Harte KJ, Sliski AP, Thomson E (2001) Targeted intra-operative radiotherapy (Targit): an innovative method of treatment for early breast cancer. Ann Oncol 12:1075–1080PubMedCrossRef

17.

Veronesi U, Gatti G, Luini A, Intra M, Orecchia R, Borgen P, Zelefsky M, McCormick B, Sacchini V (2003) Intraoperative radiation therapy for breast cancer: technical notes. Breast J 9:106–112. doi:10.1046/j.1524-4741.2003.09208.x PubMedCrossRef

18.

Ivaldi GB, Leonardi MC, Orecchia R, Zerini D, Morra A, Galimberti V, Gatti G, Luini A, Veronesi P, Ciocca M, Sangalli C, Fodor C, Veronesi U (2008) Preliminary results of electron intraoperative therapy boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women. Int J Radiat Oncol Biol Phys 72:485–493. doi:10.1016/j.ijrobp.2007.12.038 PubMedCrossRef

19.

Edmundson GK, Vicini FA, Chen PY, Mitchell C, Martinez AA (2002) Dosimetric characteristics of the MammoSite RTS, a new breast brachytherapy applicator. Int J Radiat Oncol Biol Phys 52:1132–1139. doi:10.1016/S0360-3016(01)02773-0 PubMedCrossRef

20.

Keisch M, Vicini F, Kuske RR, Hebert M, White J, Quiet C, Arthur D, Scroggins T, Streeter O (2003) Initial clinical experience with the MammoSite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys 55:289–293. doi:10.1016/S0360-3016(02)04277-3 PubMedCrossRef

21.

Lawenda BD, Taghian AG, Kachnic LA, Hamdi H, Smith BL, Gadd MA, Mauceri T, Powell SN (2003) Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant. Int J Radiat Oncol Biol Phys 56:671–680. doi:10.1016/S0360-3016(03)00071-3 PubMedCrossRef

22.

Pignol JP, Keller B, Rakovitch E, Sankreacha R, Easton H, Que W (2006) First report of a permanent breast 103Pd seed implant as adjuvant radiation treatment for early-stage breast cancer. Int J Radiat Oncol Biol Phys 64:176–181. doi:10.1016/j.ijrobp.2005.06.031 PubMedCrossRef

23.

Vicini FA, Kestin L, Chen P, Benitez P, Goldstein NS, Martinez A (2003) Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst 95:1205–1210. doi:10.1093/jnci/djg023 PubMedCrossRef

24.

King TA, Bolton JS, Kuske RR, Fuhrman GM, Scroggins TG, Jiang XZ (2000) Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is, 1, 2) breast cancer. Am J Surg 180:299–304. doi:10.1016/S0002-9610(00)00454-2 PubMedCrossRef

25.

Wazer DE, Berle L, Graham R, Chung M, Rothschild J, Graves T, Cady B, Ulin K, Ruthazer R, DiPetrillo TA (2002) Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer. Int J Radiat Oncol Biol Phys 53:889–897. doi:10.1016/S0360-3016(02)02824-9 PubMedCrossRef

26.

Paganelli G, De Cicco C, Ferrari ME, Carbone G, Pagani G, Leonardi MC, Cremonesi M, Ferrari A, Pacifici M, Di DA, De SR, Galimberti V, Luini A, Orecchia R, Zurrida S, Veronesi U (2010) Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with (90)Y-labeled biotin. Eur J Nucl Med Mol Imaging 37:203–211. doi:10.1007/s00259-009-1260-4 PubMedCrossRef

27.

Bao A, Phillips WT, Goins B, Zheng X, Sabour S, Natarajan M, Ross WF, Zavaleta C, Otto RA (2006) Potential use of drug carried-liposomes for cancer therapy via direct intratumoral injection. Int J Pharm 316:162–169. doi:10.1016/j.ijpharm.2006.02.039 PubMedCrossRef

28.

Harrington KJ, Rowlinson-Busza G, Syrigos KN, Uster PS, Vile RG, Stewart JS (2000) Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery. Clin Cancer Res 6:2528–2537PubMed

29.

Lammers T, Peschke P, Kuhnlein R, Subr V, Ulbrich K, Huber P, Hennink W, Storm G (2006) Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems. Neoplasia 8:788–795PubMedCrossRef

30.

Liu LL, Smith MJ, Sun BS, Wang GJ, Redmond HP, Wang JH (2009) Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model. Ann Surg Oncol 16:1403–1411. doi:10.1245/s10434-009-0343-6 PubMedCrossRef

31.

Liu W, MacKay JA, Dreher MR, Chen M, McDaniel JR, Simnick AJ, Callahan DJ, Zalutsky MR, Chilkoti A (2010) Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release 144:2–9. doi:10.1016/j.jconrel.2010.01.032 PubMedCrossRef

32.

Luboldt W, Pinkert J, Matzky C, Wunderlich G, Kotzerke J (2009) Radiopharmaceutical tracking of particles injected into tumors: a model to study clearance kinetics. Curr Drug Deliv 6:255–260PubMed

33.

Zentner GM, Rathi R, Shih C, McRea JC, Seo MH, Oh H, Rhee BG, Mestecky J, Moldoveanu Z, Morgan M, Weitman S (2001) Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J Control Release 72:203–215. doi:10.1016/S0168-3659(01)00276-0 PubMedCrossRef

34.

Ma G, Yang J, Zhang L, Song C (2010) Effective antitumor activity of paclitaxel-loaded poly (epsilon-caprolactone)/pluronic F68 nanoparticles after intratumoral delivery into the murine breast cancer model. Anticancer Drugs 21:261–269. doi:10.1097/CAD.0b013e32833410a2 PubMedCrossRef

35.

Kikumori T, Kobayashi T, Sawaki M, Imai T (2009) Anti-cancer effect of hyperthermia on breast cancer by magnetite nanoparticle-loaded anti-HER2 immunoliposomes. Breast Cancer Res Treat 113:435–441. doi:10.1007/s10549-008-9948-x PubMedCrossRef

36.

Kwak C, Hong SK, Seong SK, Ryu JM, Park MS, Lee SE (2005) Effective local control of prostate cancer by intratumoral injection of 166Ho-chitosan complex (DW-166HC) in rats. Eur J Nucl Med Mol Imaging 32:1400–1405. doi:10.1007/s00259-005-1892-y PubMedCrossRef

37.

Ko YT, Falcao C, Torchilin VP (2009) Cationic liposomes loaded with proapoptotic peptide D-(KLAKLAK)(2) and Bcl-2 antisense oligodeoxynucleotide G3139 for enhanced anticancer therapy. Mol Pharm 6:971–977. doi:10.1021/mp900006h PubMedCrossRef

38.

Soundararajan A, Bao A, Phillips WT, Perez R III, Goins BA (2009) [186Re]Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft model. Nucl Med Biol 36:515–524. doi:10.1016/j.nucmedbio.2009.02.004 PubMedCrossRef

39.

Wang SX, Bao A, Herrera SJ, Phillips WT, Goins B, Santoyo C, Miller FR, Otto RA (2008) Intraoperative 186Re-liposome radionuclide therapy in a head and neck squamous cell carcinoma xenograft positive surgical margin model. Clin Cancer Res 14:3975–3983. doi:10.1158/1078-0432.CCR-07-4149 PubMedCrossRef

40.

Torchilin VP (2007) Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J 9:E128–E147PubMedCrossRef

41.

Elbayoumi TA, Torchilin VP (2010) Current trends in liposome research. Methods Mol Biol 605:1–27. doi:10.1007/978-1-60327-360-2 PubMedCrossRef

42.

Phillips WT, Medina LA, Klipper R, Goins B (2002) A novel approach for the increased delivery of pharmaceutical agents to peritoneum and associated lymph nodes. J Pharmacol Exp Ther 303:11–16. doi:10.1124/jpet.102.037119 PubMedCrossRef

43.

Parker RJ, Hartman KD, Sieber SM (1981) Lymphatic absorption and tissue disposition of liposome-entrapped [14C]adriamycin following intraperitoneal administration to rats. Cancer Res 41:1311–1317PubMed

44.

Mangat S, Patel HM (1985) Lymph node localization of non-specific antibody-coated liposomes. Life Sci 36:1917–1925. doi:10.1016/0024-3205(85)90440-0 PubMedCrossRef

45.

Moghimi M, Moghimi SM (2008) Lymphatic targeting of immuno-PEG-liposomes: evaluation of antibody-coupling procedures on lymph node macrophage uptake. J Drug Target 16:586–590. doi:10.1080/10611860802228905 PubMedCrossRef

46.

Oussoren C, Storm G (2001) Liposomes to target the lymphatics by subcutaneous administration. Adv Drug Deliv Rev 50:143–156. doi:10.1016/S0169-409X(01)00154-5 PubMedCrossRef

47.

Osborne MP, Richardson VJ, Jeyasingh K, Ryman BE (1979) Radionuclide-labelled liposomes—a new lymph node imaging agent. Int J Nucl Med Biol 6:75–83. doi:10.1016/0047-0740(79)90001-9 PubMedCrossRef

48.

Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG, Stewart JS (2001) Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 7:243–254PubMed

49.

Phillips WT, Goins BA, Bao A (2009) Radioactive liposomes. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:69–83. doi:10.1002/wnan.3 PubMedCrossRef

50.

Wang SX, Bao A, Phillips WT, Goins B, Herrera SJ, Santoyo C, Miller FR, Otto RA (2009) Intraoperative therapy with liposomal drug delivery: retention and distribution in human head and neck squamous cell carcinoma xenograft model. Int J Pharm 373:156–164. doi:10.1016/j.ijpharm.2009.02.009 PubMedCrossRef

51.

French JT, Goins B, Saenz M, Li S, Garcia-Rojas X, Phillips WT, Otto RA, Bao A (2010) Interventional therapy of head and neck cancer with lipid nanoparticle-carried rhenium 186 radionuclide. J Vasc Interv Radiol. doi:10.1016/j.jvir.2010.02.027

52.

Hamoudeh M, Kamleh MA, Diab R, Fessi H (2008) Radionuclides delivery systems for nuclear imaging and radiotherapy of cancer. Adv Drug Deliv Rev 60:1329–1346. doi:10.1016/j.addr.2008.04.013 PubMedCrossRef

53.

Zweit J (1996) Radionuclides and carrier molecules for therapy. Phys Med Biol 41:1905–1914. doi:10.1088/0031-9155/41/10/004 PubMedCrossRef

54.

Bao A, Goins B, Klipper R, Negrete G, Phillips WT (2003) 186Re-liposome labeling using 186Re-SNS/S complexes: in vitro stability, imaging, and biodistribution in rats. J Nucl Med 44:1992–1999PubMed

55.

Bao A, Goins B, Klipper R, Negrete G, Mahindaratne M, Phillips WT (2003) A novel liposome radiolabeling method using 99mTc-“SNS/S” complexes: in vitro and in vivo evaluation. J Pharm Sci 92:1893–1904. doi:10.1002/jps.10441 PubMedCrossRef

56.

Li S, Goins B, Phillips WT, Bao A (2010) Remote-loading labeling of liposomes with 99mTc-BMEDA and its stability evaluation: effects of lipid formulation and pH/chemical gradient. J Liposome Res. doi:10.3109/08982101003699036

57.

Jones MN, Nicholas AR (1991) The effect of blood serum on the size and stability of phospholipid liposomes. Biochim Biophys Acta 1065:145–152. doi:10.1016/0005-2736(91)90224-V PubMedCrossRef

58.

Cullis PR, Chonn A, Semple SC (1998) Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo. Adv Drug Deliv Rev 32:3–17. doi:10.1016/S0169-409X(97)00128-2 PubMedCrossRef

59.

Moghimi SM, Moghimi M (2008) Enhanced lymph node retention of subcutaneously injected IgG1-PEG2000-liposomes through pentameric IgM antibody-mediated vesicular aggregation. Biochim Biophys Acta 1778:51–55. doi:10.1016/j.bbamem.2007.08.033 PubMedCrossRef

60.

Oussoren C, Zuidema J, Crommelin DJ, Storm G (1997) Lymphatic uptake and biodistribution of liposomes after subcutaneous injection. II. Influence of liposomal size, lipid compostion and lipid dose. Biochim Biophys Acta 1328:261–272. doi:10.1016/S0005-2736(97)00122-3 PubMedCrossRef

61.

Chambers AF, Groom AC, MacDonald IC (2002) Metastasis: dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572. doi:10.1038/nrc865 PubMedCrossRef

Titel: Post-lumpectomy intracavitary retention and lymph node targeting of 99mTc-encapsulated liposomes in nude rats with breast cancer xenograft
verfasst von: Shihong Li
Beth Goins
William T. Phillips
Marcela Saenz
Pamela M. Otto
Ande Bao
Publikationsdatum: 01.11.2011
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2011
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-010-1309-x

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