Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential.
Noninvasive or minimally invasive prediction of tumor metastatic potential would facilitate individualized cancer management. Studies were performed on a panel of human melanoma xenografts that spanned the full range of metastatic potential measured by an in vivo lung colony assay and an in vitro membrane invasion culture system. Three imaging methods potentially transferable to the clinic [dynamic contrast-enhanced (DCE) MRI, T(1(rho))-MRI, and low-temperature fluorescence imaging (measurable on biopsy specimens)] distinguished between relatively less metastatic and more metastatic human melanoma xenografts in nude mice. DCE-MRI, analyzed with the shutter-speed relaxometric algorithm and using an arterial input function simultaneously measured in the left ventricle of the mouse heart, yielded a blood transfer rate constant, K(trans), that measures vascular perfusion/permeability. K(trans) was significantly higher in the core of the least metastatic melanoma (A375P) than in the core of the most metastatic melanoma (C8161). C8161 melanoma had more blood vascular structures but fewer functional blood vessels than A375P melanoma. The A375P melanoma exhibited mean T(1(rho)) values that were significantly higher than those of C8161 melanoma. Measurements of T(1) and T(2) relaxation times did not differ significantly between these 2 melanomas. The mitochondrial redox ratio, Fp/(Fp + NADH), where Fp and NADH are the fluorescences of oxidized flavoproteins and reduced pyridine nucleotides, respectively, varied linearly with the in vitro invasive potential of the 5 melanoma cell lines (A375P, A375M, A375P10, A375P5, and C8161). This study shows that a harsh microenvironment may promote melanoma metastasis and provides potential biomarkers of metastatic potential.
Department of Radiology, School of Medicine, University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA.
Lin Z
LZ
Li
Rong
R
Zhou
He N
HN
Xu
Lily
L
Moon
Tuoxiu
T
Zhong
Eun Ju
EJ
Kim
Hui
H
Qiao
Ravinder
R
Reddy
Dennis
D
Leeper
Britton
B
Chance
Jerry D
JD
Glickson
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003287:Contrast Media; D003952:Diagnostic Imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D003287:Contrast Media