Oncologic Angiogenesis Imaging in the clinic---how and why

Abstract

The ability to control the growth of new blood vessels would be an extraordinary therapeutic tool for many disease processes. Too often, the promises of discoveries in the basic science arena fail to translate to clinical success. While several anti angiogenic therapeutics are now FDA approved, the envisioned clinical benefits have yet to be seen. The ability to clinically non-invasively image angiogenesis would potentially be used to identify patients who may benefit from anti-angiogenic treatments, prognostication/risk stratification and therapy monitoring. This article reviews the current and future prospects of implementing angiogenesis imaging in the clinic.

FIGURE 1

65-year-old man with serum prostate specific antigen (PSA) level of 9.2 ng/dl. Axial T2 weighted MRI shows a vague low signal intensity lesion in the left mid-base peripheral zone (arrow) (A); ADC maps derived from diffusion weighted MRI shows restricted diffusion within the left peripheral zone lesion (arrow) (B); raw DCE MR image demonstrates fast and early enhancement within the left peripheral zone lesion (marked in red) (C) (C1: arterial input function curve, C2: Gd concentration curve of the left peripheral zone lesion); Ktrans (S) and kep (E) maps derived from DCE MRI also localizes the left peripheral zone lesion (arrow).

FIGURE 2

57 year-old male with non-squamous cell lung cancer lesion in the upper lobe of the left lung (red region of interest (ROI). Initially high K^trans and k_ep are seen in the baseline parametric maps, with the red coloring representing high flow (right column, second and third rows). Following Sorafenib treatment, the lesion size decreased and the K^trans and k_ep values are reduced.

FIGURE 3

Figure 3a and 3b. Images of α4_vβ₃ integrin PET/CT imaging performed after the injection of ¹⁸F-Flucilatide in two patients with melanoma. In FIGURE 3a., diffuse high uptake (SUV_max 6.4) in the large soft tissue metastasis can be seen (cross hairs). The metastatic melanoma focus in Figure 3b. shows a central photon deficit and mild (SUV_max of 3.0) ¹⁸F-Flucilatide uptake around the periphery

FIGURE 3

Figure 3a and 3b. Images of α4_vβ₃ integrin PET/CT imaging performed after the injection of ¹⁸F-Flucilatide in two patients with melanoma. In FIGURE 3a., diffuse high uptake (SUV_max 6.4) in the large soft tissue metastasis can be seen (cross hairs). The metastatic melanoma focus in Figure 3b. shows a central photon deficit and mild (SUV_max of 3.0) ¹⁸F-Flucilatide uptake around the periphery

FIGURE 4

A PET/CT volume rendering of a mouse thorax, imaged with ¹⁸FDG, imaging glucose metabolism (left) and ⁶⁴Cu knottin 2.5F, imaging α_vβ₃ integrin expression(right). A lung nodule obscured by physiologic cardiac uptake on the ¹⁸FDG (right) imaged is clearly visualized in the ⁶⁴Cu knottin 2.5F (left) image. Activity beneath the diaphragm represents physiology activity. Reprinted (caption modified) from (39). Nielsen CH, Kimura RH, Withofs N, et al. PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA- knottin peptide. Cancer Res. Nov 15 2010;70(22):9022–9030.

FIGURE 5

Non-invasive PET/CT images of angiogenesis induced by hindlimb ischemia in a murine model. (A) Non-targeted dendritic nanoprobes. (B) Uptake of α_vβ₃ integrin targeted dendritic nanoprobes. Note accumulation of α_vβ₃ integrin targeted dendritic nanoprobes in the right ischemic hindlimb (box in B), when compared with the lack of uptake of the non-targeted agent (box in A). The structure and biodegradably nature of this nanoprobe may make it useful in developing a non-toxic, targeted combined therapy/imaging agent. Reproduced with modifications, from Almutairi A, Rossin R, Shokeen M, et al. Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis. Proc Natl Acad Sci U S A. Jan 20 2009;106(3):685–690. with permission.