Multimodality molecular imaging of CD105 (Endoglin) expression

Abstract

Since most solid tumor growth depends on angiogenesis, non-invasive imaging of tumor angiogenesis can allow for much earlier diagnosis and better prognosis of cancer, as well as more accurate treatment monitoring, which will eventually lead to personalized molecular medicine. CD105, also known as endoglin, is required for endo-thelial cell proliferation. The currently accepted standard method for quantifying tumor angiogenesis is to assess microvessel density based on CD105 staining, which has been shown to be an independent prognostic factor for survival in patients of almost all solid tumor types. In this review, we will summarize the progress to date on multimo-dality molecular imaging of CD105 expression during tumor angiogenesis which includes targeted contrast-enhanced ultrasound, molecular magnetic resonance, near-infrared fluorescence, single-photon emission computed tomography, and positron emission tomography. Although molecular imaging of CD105 expression is surprisingly understudied, non-invasive imaging of CD105 expression has already been achieved with every single molecular imaging modality. In the future, significant research effort should be directed towards non-invasive visualization of CD105 expression, such as quantitative imaging, the use of long-lived isotopes for antibody-based imaging, development of peptide, small molecule, or antibody fragment-based imaging agents, multimodality imaging of CD105 expression with a single agent, the application of nanotechnology, among others.

Keywords: CD105 (Endoglin); Tumor angiogenesis; anti-angiogenic therapy; cancer; molecular imaging; monoclonal antibody (mAb); positron emission tomography (PET); single-photon emission computed tomography (SPECT).

Figure 1

Molecular MRI of CD105 expression. T₁-weighted images at different time points post-injection of various contrasts agents are shown. *: subcutaneous tumor. Adapted from reference [42].

Figure 2

Optical imaging of CD105 expression. The 4T1 murine breast cancer tumors (arrowheads) in Balb/c mice can be clearly visualized in a small animal optical scanner after intravenous injection of 800CW-TRC105. The CD105 specificity was confirmed by the much lower tumor uptake of 800CW or 800CW-TRC105 when co-injected with TRC105 (denoted as “800CW-TRC105 + Blocking”).

Figure 3

PET imaging of CD105 expression. A. Coronal PET images of 4T1 tumor-bearing mice at 4 and 24 h post-injection of ⁶⁴Cu-DOTA-TRC105 or ⁶⁴Cu -DOTA-cetuximab. B. CT and PET/CT images of ⁶⁴Cu -DOTA-TRC105 in 4T1 tumor-bearing mice at 24 h post-injection. Arrowheads indicate the 4T1 tumors.