Two-photon fluorescence correlation microscopy reveals the two-phase nature of transport in tumors.
Transport parameters determine the access of drugs to tumors. However, technical difficulties preclude the measurement of these parameters deep inside living tissues. To this end, we adapted and further optimized two-photon fluorescence correlation microscopy (TPFCM) for in vivo measurement of transport parameters in tumors. TPFCM extends the detectable range of diffusion coefficients in tumors by one order of magnitude, and reveals both a fast and a slow component of diffusion. The ratio of these two components depends on molecular size and can be altered in vivo with hyaluronidase and collagenase. These studies indicate that TPFCM is a promising tool to dissect the barriers to drug delivery in tumors.
Alexandrakis
George
G
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Brown
Edward B
EB
Tong
Ricky T
RT
McKee
Trevor D
TD
Campbell
Robert B
RB
Boucher
Yves
Y
Jain
Rakesh K
RK
D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
D005456:Fluorescent Dyes