title: Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.
abstract: Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Bryan Q
authors.initials: BQ
authors.lastname: Spring
authors.forename: Adnan O
authors.initials: AO
authors.lastname: Abu-Yousif
authors.forename: Akilan
authors.initials: A
authors.lastname: Palanisami
authors.forename: Imran
authors.initials: I
authors.lastname: Rizvi
authors.forename: Xiang
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Mai
authors.forename: Sriram
authors.initials: S
authors.lastname: Anbil
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Sears
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Mensah
authors.forename: Ruth
authors.initials: R
authors.lastname: Goldschmidt
authors.forename: S Sibel
authors.initials: SS
authors.lastname: Erdem
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D016503:Drug Delivery Systems / Q000379:methods*; D004724:Endoscopy / Q000379:methods; D005260:Female; D005453:Fluorescence; D018796:Immunoconjugates / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods; D008027:Light; D051379:Mice; D015166:Monitoring, Immunologic / Q000379:methods*; D061206:Neoplasm Micrometastasis / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000473:pathology*; D010789:Phototherapy / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates
keywords: activatable imaging agent; activatable therapeutic agent; molecular imaging; ovarian cancer; photodynamic therapy