Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Abstract

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Fe₃O₄<em>@</em>Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells

“…4 These aggressive brain tumors grow invasively and cause discernible neurologic symptoms within months with an extremely poor prognosis. Even treated with aggressive open surgery combined with adjuvant chemo/ radiotherapy, the median survival time is still ,15 months, [5][6][7][8] and current treatment paradigms appear to have reached their maximum benefit. Therefore, for decades, considerable efforts have been devoted to developing more effective antitumor agents and better strategies for targeting human glioma.…”

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

“…23 However, it is not enough to improve the specificity of chemotherapy drugs alone. On the one hand, because of the presence of several biological barriers, such as the mononuclear phagocyte system, 24 blood-brain barrier (BBB), 25,26 kidney filtration, 27,28 and so on, chemotherapy drugs have difficulty in reaching the tumor site and may not reach the effective concentration in some tissues. On the other hand, the role of chemotherapy drugs will also be affected by human metabolism.…”

A Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an 18[F]-Positron Emitting, Fluorescent Derivative of Dasatinib

“…The murine model, and the PET and FL visibility of [ 18 F]- 1 is applied to CED in this report, but it should be noted that these methodologies should have utility in quantitating or contrasting drug delivery in other popular new methods, such as focused ultrasound (FU) or mannitol assisted delivery (1,16). The described methodology should have additional utility in advanced, combined drug delivery efforts, such as FU-CED, a promising delivery combination.…”

“…Positron emission tomography (PET) can be more sensitive than MR contrast (8,9,15), making PET uniquely useful for tracking chemotherapeutics at nanomolar concentration. This is clear from recent efforts focused on 124 I-tagged antibodies, which have both a therapeutic effect in tumor-specific antigen targeting, and can be imaged by PET (3,16,17). …”