Tumor-Targeted Quantum Dots Can Help Surgeons Find Tumor Boundaries

Abstract

Despite surgical advances and recent progress in adjuvant therapies, the prognosis for patients with malignant brain tumors such as glioblastoma multiforme has remained poor, and the neurological deterioration suffered by most patients as a consequence of tumor progression is dramatic and severe. In addition, malignant brain tumors have >>95% recurrence close to the primary site of initial resection. Unfortunately, standard imaging techniques do not permit the intraoperative identification of individual or small clusters of residual tumor cells, precluding their selective removal while sparing the surrounding normal brain tissue. In this report, we show that quantum dots (QDs) coupled to epidermal growth factor (EGF) or anti-EGF receptor receptor (EGFR, Her1) specifically and sensitively label glial tumor cells in cell culture, glioma mouse models, and human brain-tumor biopsies. A clear demarcation between brain and tumor tissue at the macroscopic as well as the cellular level is provided by the fluorescence emission of the QDs.

Review of Neurosurgical Fluorescence Imaging Methodologies

“…Wang et al coated QDs with anti-EGFR antibodies and found that the targeted QDs localized selectively in tumors expressing EGFR within 30 minutes of intravenous administration [71]. Additionally, Arndt-Jovin et al demonstrated that clear demarcation between normal brain and tumor tissue could be observed with QDs labeled with either EGF or anti-EGFR (Her1) in cell culture, mouse models and human brain-tumor biopsy sections [70]. Although there is advantageous targeting with EGF-bound fluorophores, it must be noted that this only occurs with tumors overexpressing EGF and EGFR.…”

“…Within the last several years there have been many examples of quantum dots used for the determination of tumor boundaries using both passive [68–69] and targeted delivery methods. [70–72]. Although QDs provide very high contrast and tumor localization, the largest drawback to their use is that the long term effects of QD administration are generally unknown and strongly debated as clearance from both tissue and body is an important factor in toxicity [73].…”

A low molecular weight PSMA-based fluorescent imaging agent for cancer

“…All that is needed is a light-emitting diode to excite the fluorophore, which can be administered systemically or “painted” on the tissue directly. More recent incarnations of PDD have used quantum dots [11], and more advanced dyes, such as indocyanine green (ICG) [12], which emit in the near-infrared (NIR) region of the spectrum, enabling reasonable tissue penetration of emitted (and detected) light. Applications have included nontargeted approaches, such as preoperative evaluation of the vascular integrity of surgical flaps or identification of nodules of hepatocellular carcinoma [13].…”

The Application of Nanomaterials in Diagnosis and Treatment for Malignant Primary Brain Tumors

“…76 QDs and CNTs have not yet been applied to experimental orthotopic malignant primary brain tumors as diagnostic agents. 130,131 Apart from these inorganic NPs, some organic nanovehicles, i.e., dendrimers and nanogels, have also found roles in intraoperative brain tumor delineation. 48,49,[65][66][67] Yan et al have developed a multimodal optical/paramagnetic dendrimer to load gadolinium and Cy5.5 across the BBB and image glioma with high-sensitivity in vivo.…”