**4.3. VEG/PF**

Vascular endothelial growth/permeability factor (VEG/PF) is a 40 kda disulphide-linked dimeric glycoprotein that is active in increasing blood vessel permeability, endothelial cell growth and angiogenesis. These properties suggest that the expression of VEG/PF by tumor cells could contribute to the increased neovascularization and vessel permeability that are associated with tumor vasculature. The cDNA sequence of VEG/PF from human U937 cells was shown to code for a 189-amino acid polypeptide that is similar in struc‐ ture to the B chain of PDGF-B and other PDGF-B-related proteins. The overall identity with PDGF-B is 18%. However, all eight of the cysteines in PDGF-B were conserved in human VEG/PF, an indication that the folding of the two proteins is probably similar. Clusters of basic amino acids in the COOH-terminal halves of human VEG/PF and PDGF-B are also prevalent. Thus, VEG/PF appears to be related to the PDGF/v-sis family of proteins [58].

**6. Perfusion CT**

The fundamental principle of perfusion CT is based on the temporal changes in tissue at‐ tenuation after intravenous administration of iodinated contrast material (CM). This en‐ hancement depends on the tissue iodine concentration, existing a direct linear relationship

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Recent progress in multidetector CT technology has enabled the rapid scanning of large ana‐ tomic volumes with high resolution. In perfusion CT, repeated series of images of the vol‐ ume analyzed are performed in quick succession before, during and after intravenous administration of CM. The ensuing tissue enhancement can be divided into two phases based on CM distribution: a initial phase where the enhancement is attributable to the distri‐ bution of contrast within the intravascular space ("first pass", lasting 40-60 secs. from the contrast arrival), and a second phase as contrast diffuses from the intravascular to the ex‐ travascular compartment across the capillary basement membrane (2-5 minutes duration). To objectively quantify the "real" perfusion parameters of tissues from the density differ‐ ence produced by the contribution of contrast material, a mathematic model is applied to the dynamic CT data. The quantitative parameters generated include blood volume (BV),

Perfusion CT is a biomarker for angiogenesis that have been validated with other surrogate markers, such as VEGF levels, tumor perfusion and microvascular density (Fig 4) [63]. There has been a gradual increase of its use in oncology, ranging the wide spectrum of clinical ap‐ plications of this technique, from lesion characterization, (differentiation between benign and malignant lesions), to prognostic information based on tumor vascularity and monitor‐ ing therapeutic effects of chemoradiation and antiangiogenic drugs. In a recent study using a 320-detector row CT, Ohno et al. concluded that perfusion CT has the potential to be more specific and accurate than PET/CT for differentiating malignant from benign pulmonary nodules [64]. Another study have also shown that in patients with NSCLC treated with sora‐ fenib and erlotinib, early changes in tumor blood flow were predictive of objective response

**Figure 4.** Parametric maps of perfusion CT studies representing blood flow in two different patients with NSCLC. (A) Tumor with very low perfusion depicted in blue and (B) a highly vascularized neoplasm showing yellow and red zones (scale at left).

between contrast concentration and CT enhancement [62].

blood flow (BF), mean transit time and capillary permeability surface.

and tended to indicate a longer progression-free survival [65].
