Table 1.

Selected trials of angiogenesis inhibitors evaluated by DCE-MRI

Tumor group*AgentnAcquisitionAIFDCE-MRI biomarkerROI§Principal findingsReference
Anti-VEGF antibody
    MixedHuMV83320Three-dimensionalMeasuredKtrans, kep, vpPixel basedReduction in kep but no dose relationshipJayson et al. (33)
    BreastBevacizumab20MeasuredKtrans, veWhole tumorReduction in Ktrans of 34%Wedam et al. (49)
Tyrosine kinase inhibitor
    GBMPTK/ZK14T1- and T2*-weightedKi, CBVDose-dependent reduction in Ki predicts progressionConrad et al. (29)
    CRCPTK/ZK26Two-dimensional single sliceAssumed (FH)KiWhole tumorDose-dependent reduction in Ki predicts RR and progressionMorgan et al. (36)
    MixedPTK/ZK27Two-dimensional single sliceAssumed (FH)KiWhole tumorDose-dependent reduction in Ki predicts RR and progressionMross et al. (37)
    MixedAZD217124Two-dimensional single sliceIAUGCWhole tumorReduction in IAUC of ≥40% defined doseDrevs et al. (30)
    GBMAZD217116Three-dimensional and T2*-weightedKtrans, ve, CBV, CBFPixel basedReduction in Ktrans and veBatchelor et al. (28)
    MixedAG-01373617Three-dimensionalMeasuredIAUGC, KtransWhole tumorDose-dependent reduction in IAUGC and KtransLiu et al. (34)
    RCCBAY43-900612Ktrans, veReduction in Ktrans predicts RR and PFSO'Dwyer et al. (42)
    MixedBIBF112035Two-dimensional multisliceAssumed (FH)IAUGC, Ktrans, kepNo consistent relationship with clinical measuresPadhani et al. (44)
Recombinant human endostatin
    MixedrhEndostatin10Two-dimensional two sliceMeasuredKtrans, vePixel basedNo change in DCE-MRI biomarkersEder et al. (31)
Anti-PDGFR-β antibody Fab′
    MixedCDP8608Three-dimensionalMeasuredIAUGC, Ktrans, ve, vpPixel basedNo change in DCE-MRI biomarkersJayson et al. (32)
Anti-αv integrin
    MixedCNTO 9522Three-dimensionalMeasuredIAUGC, Ktrans, ve, vpPixel basedHistogram showed difference in group KtransWatson et al. (89)
    GBMEMD 12197421T2*-weightedMeasuredCBV, CBFPixel basedReduction in gradient peak and enhancementAkella et al. (27)
Flavonoid
    MixedDMXAA16Two-dimensional multisliceNo modelSI metricsPixel basedReduction in SI metricsGalbraith et al. (54)
Antitubulin combretastatin analogue
    MixedCA-4-P7Two-dimensional single sliceNo modelSI metricsWhole tumorReduction in gradient peak and enhancementDowlatti et al. (51)
    MixedCA-4-P18Two-dimensional multisliceAssumed (W)IAUGC, Ktrans, vePixel basedDose-dependent reduction in Ktrans defined doseGalbraith et al. (53)
    MixedCA-4-P10Three-dimensionalKtrans, veWhole tumorNo consistent findingsStevenson et al. (56)
Colchicine analogue
    MixedZD61269Three-dimensionalIAUGCPixel basedDose-dependent reduction in IAUGCEvelhoch et al. (52)
  • NOTE: Not all details were provided in some studies.

    Abbreviations: GBM, glioblastoma multiforme; CRC, colorectal carcinoma; RCC, renal cell carcinoma; VEGF, vascular endothelial growth factor; PDGFR-β, platelet-derived growth factor receptor-β; FH, Fritz-Hansen method; W, Weinmann method; RR, response rate; PFS, progression-free survival; EES, extracellular extravascular space.

  • * Tumors were either mixed solid group, breast, glioblastoma multiforme, or colorectal or renal cell carcinoma.

  • AIF was either measured or assumed by the Fritz-Hansen or Weinmann methods.

  • DCE-MRI biomarkers include (in table order) Ktrans (volume transfer coefficient), kep (rate constant), vp (blood plasma volume), ve (volume of the EES), Ki (unidirectional influx), IAUGC (initial area under the gadolinium contrast agent concentration-time curve), CBV, CBF (cerebral blood flow), or SI (signal intensity) metrics.

  • § ROI analysis was either on a whole-tumor basis or pixel based.

  • All T1-weighted acquisitions were at 1.5 T except Batchelor et al. (28), done at 3 T.