Chemodosimetry of in vivo tumor liposomal drug concentration using MRI.
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 T(1)-weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T(1) 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 T(1) 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.
Viglianti
Benjamin L
BL
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Ponce
Ana M
AM
Michelich
Charles R
CR
Yu
Daohai
D
Abraham
Sheela A
SA
Sanders
Linda
L
Yarmolenko
Pavel S
PS
Schroeder
Thies
T
MacFall
James R
JR
Barboriak
Daniel P
DP
Colvin
O Michael
OM
Bally
Marcel B
MB
Dewhirst
Mark W
MW
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics*; D005354:Fibrosarcoma / Q000378:metabolism*; D006979:Hyperthermia, Induced; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008081:Liposomes / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000493:pharmacokinetics*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013431:Sulfates; D013696:Temperature; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D017895:Manganese Compounds; D013431:Sulfates; D004317:Doxorubicin; C039798:manganese sulfate