Molecular imaging for cancer diagnosis and surgery

Abstract

Novel molecular imaging techniques have the potential to significantly enhance the diagnostic and therapeutic approaches for cancer treatment. For solid tumors in particular, novel molecular enhancers for imaging modalities such as US, CT, MRI and PET may facilitate earlier and more accurate diagnosis and staging which are prerequisites for successful surgical therapy. Enzymatically activatable "smart" molecular MRI probes seem particularly promising because of their potential to image tumors before and after surgical removal without re-administration of the probe to evaluate completeness of surgical resection. Furthermore, the use of "smart" MR probes as part of screening programs may enable detection of small tumors throughout the body in at-risk patient populations. Dual labeling of molecular MR probes with fluorescent dyes can add real time intraoperative guidance facilitating complete tumor resection and preservation of important structures. A truly theranostic approach with the further addition of therapeutic agents to the molecular probe for adjuvant therapy is conceivable for the future.

Keywords: Cancer diagnosis; Fluorescence guided surgery; Molecular imaging.

Figure 1

Preoperative MRI image of a mouse injected with gadolinium and Cy5 dual-labeled ACPPD showing contrast uptake in tumor (A, black arrow pointing to the tumor). Repeat MRI (B) following tumor removal surgery showed a small area of tissue with increased gadolinium uptake (C inset, white arrowhead). Histological analysis confirmed the presence of cancer cells (C). Scale bar 100 μm. (Adapted and reprinted from reference .)

Figure 2. Fluorescent labeling facilitates intraoperative tumor identification

In a parotid gland cancer model of a mouse, no tumor is immediately apparent in the white light image (A, the yellow outline indicates the extent of the tumor, white arrows point to branches of the facial nerve). Under fluorescence guidance with a fluorescently labeled ACPP, the tumor and its extent are easily identifiable (B: fluorescent image, C: color overlay).

Figure 3. Enhanced nerve visualization

The identification of the branches of a right facial nerve of a mouse is enhanced by fluorescent molecular probe labeling (B) compared to the white light image (A). Large superficial branches (white arrows) can be easily identified even under white light alone, visualization of smaller branches is clearly improved by fluorescence imaging.