Phenotyping of tumor biology in patients by multimodality multiparametric imaging: relationship of microcirculation, alphavbeta3 expression, and glucose metabolism.
Both dynamic contrast-enhanced (DCE) MRI and PET provide quantitative information on tumor biology in living organisms. However, imaging biomarkers often neglect tissue heterogeneity by focusing on distributional summary statistics. We analyzed the spatial relationship of α(v)β(3) expression, glucose metabolism, and perfusion by PET and DCE MRI, focusing on tumor heterogeneity.


METHODS
Thirteen patients with primary or metastasized cancer (non-small cell lung cancer, n = 9; others, n = 4) were examined with DCE MRI and with PET using (18)F-galacto-RGD and (18)F-FDG. Twenty-three different regions of interest were defined by cluster analysis based on the heterogeneity of tracer uptake. In these regions, the initial area under the gadopentetate dimeglumine concentration-time curve (IAUGC), as well as the regional blood volume (rBV) and regional blood flow (rBF), were estimated from DCE MRI and correlated with standardized uptake values from PET.


RESULTS
Regions with simultaneously high uptake of (18)F-galacto-RGD and (18)F-FDG showed higher functional MRI data (IAUGC, 0.35 ± 0.04 mM·s; rBF, 70.2 ± 12.7 mL/min/100 g; rBV, 23.3 ± 2.7 mL/100 g) than did areas with low uptake of both tracers (IAUGC, 0.15 ± 0.04 mM·s [P < 0.01]; rBF, 28.3 ± 10.8 mL/min/100 g; rBV, 9.9 ± 1.9 mL/100 g [P < 0.01]). There was a weak to moderate correlation between the functional MRI parameters and (18)F-galacto-RGD (r = 0.30-0.62) and also (18)F-FDG (r = 0.44-0.52); these correlations were significant (P < 0.05), except for (18)F-galacto-RGD versus rBF (P = 0.17).


CONCLUSIONS
These data show that multiparametric assessment of tumor heterogeneity is feasible by combining PET and MRI. Perfusion is highest in tumor areas with simultaneously high α(v)β(3) expression and high glucose metabolism and restricted in areas with both low α(v)β(3) expression and low glucose metabolism. The current limitations resulting from imaging with separate scanners might be overcome by future hybrid PET/MRI scanners.
Department of Radiology, Technische Universität München, Munich, Germany.
Stephan
S
Metz
Carl
C
Ganter
Sylvie
S
Lorenzen
Sandra
S
van Marwick
Ken
K
Herrmann
Florian
F
Lordick
Stephan G
SG
Nekolla
Ernst J
EJ
Rummeny
Hans-Jürgen
HJ
Wester
Gunnar
G
Brix
Markus
M
Schwaiger
Ambros J
AJ
Beer
D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D003952:Diagnostic Imaging; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography; D047368:Tumor Burden
D039302:Integrin alphaVbeta3; D019788:Fluorodeoxyglucose F18; D005947:Glucose