title: 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.
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. umt2001@med.cornell.edu.
authors.forename: Umberto
authors.initials: U
authors.lastname: Tosi
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. csm2002@med.cornell.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Marnell
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. rkc2003@med.cornell.edu.
authors.forename: Raymond
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, China. chocs@ha.org.hk.
authors.forename: William C
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Department of Radiology, Molecular Imaging Innovations Institute, Weill Cornell Medicine, New York, NY 10065, USA. rct2001@med.cornell.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Ting
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. ubm2002@med.cornell.edu.
authors.forename: Uday B
authors.initials: UB
authors.lastname: Maachani
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA. mmsouwei@med.cornell.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Souweidane
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D057054:Molecular Imaging / Q000379:methods; D058990:Molecular Targeted Therapy; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers
keywords: blood–brain-barrier; central nervous system (CNS) tumors; convection-enhanced delivery; theranostics