Chemodosimetry of in vivo tumor liposomal drug concentration using MRI
Benjamin L. Viglianti
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorAna M. Ponce
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorCharles R. Michelich
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorDaohai Yu
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorSheela A. Abraham
Advanced Therapeutics-Medical Oncology, BC Cancer Agency, Vancouver, Canada
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Search for more papers by this authorLinda Sanders
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorPavel S. Yarmolenko
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorThies Schroeder
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorJames R. MacFall
Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorDaniel P. Barboriak
Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorO. Michael Colvin
Department of Medicine and Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorMarcel B. Bally
Advanced Therapeutics-Medical Oncology, BC Cancer Agency, Vancouver, Canada
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Search for more papers by this authorCorresponding Author
Mark W. Dewhirst
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Duke University Medical Center, Department of Radiation of Oncology, MSRB 201, Box 3455, Durham, NC 27710===Search for more papers by this authorBenjamin L. Viglianti
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorAna M. Ponce
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorCharles R. Michelich
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Search for more papers by this authorDaohai Yu
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorSheela A. Abraham
Advanced Therapeutics-Medical Oncology, BC Cancer Agency, Vancouver, Canada
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Search for more papers by this authorLinda Sanders
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorPavel S. Yarmolenko
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorThies Schroeder
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorJames R. MacFall
Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorDaniel P. Barboriak
Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorO. Michael Colvin
Department of Medicine and Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorMarcel B. Bally
Advanced Therapeutics-Medical Oncology, BC Cancer Agency, Vancouver, Canada
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Search for more papers by this authorCorresponding Author
Mark W. Dewhirst
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
Duke University Medical Center, Department of Radiation of Oncology, MSRB 201, Box 3455, Durham, NC 27710===Search for more papers by this authorAbstract
Effective cancer chemotherapy depends on the delivery of therapeutic drugs to cancer cells at cytotoxic concentrations. However, physiologic barriers, such as variable vessel permeability, high interstitial fluid pressure, and heterogeneous perfusion, make it difficult to achieve that goal. Efforts to improve drug delivery have been limited by the lack of noninvasive tools to evaluate intratumoral drug concentration and distribution. Here we demonstrate that tumor drug concentration can be measured in vivo using T1-weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T1 relaxation times and Mn:DOX loading ratios, as previously described. Two independent validations by high-performance liquid chromatography (HPLC) and histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant linear relationship between DOX concentrations determined using T1 and those measured invasively. This method of imaging exhibits potential for real-time evaluation of chemotherapeutic protocols and prediction of tumor response on an individual patient basis. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc.
REFERENCES
- 1 Needham D, Anyarambhatla G, Kong G, Dewhirst MW. A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 2000; 60: 1197–1201.
- 2 Needham D, Dewhirst MW. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev 2001; 53: 285–305.
- 3 Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 2000; 60: 6950–6957.
- 4 Viglianti BL, Abraham SA, Michelich CR, Yarmolenko PS, MacFall JR, Bally MB, Dewhirst MW. In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: illustration of targeted delivery. Magn Reson Med 2004; 51: 1153–1162.
- 5 Abraham SA, Edwards K, Karlsson G, MacIntosh S, Mayer LD, McKenzie C, Bally MB. Formation of transition metal-doxorubicin complexes inside liposomes. Biochim Biophys Acta 2002; 1565: 41–54.
- 6 Morgan L, Nolle A. Proton spin relation in aqueous solutions of paramagnetic ions II: Cr+++, Mn++. Ni++, Cu++, and Gd++. J Chem Phys 1959; 31: 365.
- 7 Liang Z-P, Lauterbur PC, IEEE Engineering in Medicine and Biology Society. Principles of magnetic resonance imaging: a signal processing perspective. Bellingham, WA: SPIE Optical Engineering Press/IEEE Press; 2000. xv, 416 p.
- 8 Wehrli FW, Shaw D, Kneeland JB. Biomedical magnetic resonance imaging: principles, methodology, and applications. New York: John Wiley & Sons, Inc., 1988. xvii, 601 p.
- 9 Grant JP, Wells JrSA. Tumor resistance in rats immunized to fetal tissues. J Surg Res 1974; 16: 533–540.
- 10 Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res 2000; 60: 4440–4445.
- 11 Kong G, Braun RD, Dewhirst MW. Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature. Cancer Res 2001; 61: 3027–3032.
- 12 Dafni H, Gilead A, Nevo N, Eilam R, Harmelin A, Neeman M. Modulation of the pharmacokinetics of macromolecular contrast material by avidin chase: MRI, optical, and inductively coupled plasma mass spectrometry tracking of triply labeled albumin. Magn Reson Med 2003; 50: 904–914.
- 13 Mayer LD, Hope MJ, Cullis PR, Janoff AS. Solute distributions and trapping efficiencies observed in freeze-thawed multilamellar vesicles. Biochim Biophys Acta 1985; 817: 193–196.
- 14 Fenske DB, Wong KF, Maurer E, Maurer N, Leenhouts JM, Boman N, Amankwa L, Cullis PR. Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients. Biochim Biophys Acta 1998; 1414: 188–204.
- 15 Tardi P, Choice E, Masin D, Redelmeier T, Bally M, Madden TD. Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. Cancer Res 2000; 60: 3389–3393.
- 16 Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, Lacy EK, Zhang H, Robertson JD, Wickline SA, Lanza GM. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 Tesla magnetic resonance imaging. Cancer Res 2003; 63: 5838–5843.
- 17 de Lussanet QG, Backes WH, Griffioen AW, van Engelshoven JM, Beets-Tan RG. Gadopentetate dimeglumine vs. ultrasmall superparamagnetic iron oxide for dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon carcinoma in mice. Radiology 2003; 229: 429–438.
- 18 Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH, Weissleder R. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 2003; 63: 6838–6846.
- 19 Shen F, Poncet-Legrand C, Somers S, Slade A, Yip C, Duft AM, Winnik FM, Chang PL. Properties of a novel magnetized alginate for magnetic resonance imaging. Biotechnol Bioeng 2003; 83: 282–292.
- 20 Sinha VR, Goyal V, Bhinge JR, Mittal BR, Trehan A. Diagnostic microspheres: an overview. Crit Rev Ther Drug Carrier Syst 2003; 20: 431–458.
- 21 Ulrich CM, Robien K, McLeod HL. Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer 2003; 3: 912–920.
- 22 Lymberis SC, Parhar PK, Katsoulakis E, Formenti SC. Pharmacogenomics and breast cancer. Pharmacogenomics 2004; 5: 31–55.
- 23 Marsh S, McLeod HL. Cancer pharmacogenetics. Br J Cancer 2004; 90: 8–11.
- 24 El-Kareh AW, Secomb TW. A mathematical model for cisplatin cellular pharmacodynamics. Neoplasia 2003; 5: 161–169.
- 25 Brooks KR, To K, Joshi MB, Conlon DH, Herndon 2ndJE, D'Amico TA, Harpole JrDH. Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection. Ann Thorac Surg 2003; 76: 187–193; discussion 193.
- 26 Loni L, Del Tacca M, Danesi R. Pharmacogenetics of anticancer drugs in non-Hodgkin lymphomas. Br J Cancer 2001; 85: 1425–1431.
- 27 CA Perez, EC Halperin, LW Brady, RK Schmidt-Ullrich, editors. Principles and practice of radiation oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 1998. 2527 p.
- 28 Bhatnagar A, Hustinx R, Alavi A. Nuclear imaging methods for non-invasive drug monitoring. Adv Drug Deliv Rev 2000; 41: 41–54.
- 29 Matteucci ML, Anyarambhatla G, Rosner G, Azuma C, Fisher PE, Dewhirst MW, Needham D, Thrall DE. Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas. Clin Cancer Res 2000; 6: 3748–3755.
- 30 Leander P, Mansson S, Ege T, Besjakov J. CT and MR imaging of the liver using liver-specific contrast media. A comparative study in a tumour model. Acta Radiol 1996; 37(3 Pt 1): 242–249.
- 31 Schwendener RA, Wuthrich R, Duewell S, Wehrli E, von Schulthess GK. A pharmacokinetic and MRI study of unilamellar gadolinium-, manganese-, and iron-DTPA-stearate liposomes as organ-specific contrast agents. Invest Radiol 1990; 25: 922–932.
- 32 Suga K, Mikawa M, Ogasawara N, Okazaki H, Matsunaga N. Potential of Gd-DTPA-mannan liposome particles as a pulmonary perfusion MRI contrast agent: an initial animal study. Invest Radiol 2001; 36: 136–145.
- 33
Chu WJ,
Simor T,
Elgavish GA.
In vivo characterization of Gd(BME-DTTA), a myocardial MRI contrast agent: tissue distribution of its MRI intensity enhancement, and its effect on heart function.
NMR Biomed
1997;
10:
87–92.
10.1002/(SICI)1099-1492(199704)10:2<87::AID-NBM438>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- 34 Unger E, Fritz T, Shen DK, Wu G. Manganese-based liposomes. Comparative approaches. Invest Radiol 1993; 28: 933–938.
- 35 Unger E, Shen DK, Wu GL, Fritz T. Liposomes as MR contrast agents: pros and cons. Magn Reson Med 1991; 22: 304–308; discussion 313.
- 36
Bulte JW,
de Cuyper M,
Despres D,
Frank JA.
Short- vs. long-circulating magnetoliposomes as bone marrow-seeking MR contrast agents.
J Magn Reson Imaging
1999;
9:
329–335.
10.1002/(SICI)1522-2586(199902)9:2<329::AID-JMRI27>3.0.CO;2-Z CAS PubMed Web of Science® Google Scholar
- 37 Fossheim SL, Fahlvik AK, Klaveness J, Muller RN. Paramagnetic liposomes as MRI contrast agents: influence of liposomal physicochemical properties on the in vitro relaxivity. Magn Reson Imaging 1999; 17: 83–89.
- 38 Bacic G, Niesman MR, Bennett HF, Magin RL, Swartz HM. Modulation of water proton relaxation rates by liposomes containing paramagnetic materials. Magn Reson Med 1988; 6: 445–458.
- 39 Niesman MR, Bacic GG, Wright SM, Swartz HJ, Magin RL. Liposome encapsulated MnCl2 as a liver specific contrast agent for magnetic resonance imaging. Invest Radiol 1990; 25: 545–551.
