title: Platinum compounds for high-resolution in vivo cancer imaging.
abstract: Platinum(II) compounds, principally cisplatin and carboplatin, are commonly used front-line cancer therapeutics. Despite their widespread use and continued interest in the development of new derivatives, including nanoformulations with improved properties, it has been difficult to visualize platinum compounds in live subjects, in real time, and with subcellular resolution. Here, we present four novel cisplatin- and carboplatin-derived fluorescent imaging compounds for quantitative intravital cancer imaging. We conjugated 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-daiza-s-indacene (BODIPY) to Pt(II) complexes to generate derivatives with robust in vivo fluorescence and retained DNA-damaging and cytotoxic properties. We successfully applied these compounds to image pharmacokinetics and tumor uptake in a xenograft cancer mouse model. By using a genetic reporter of single-cell DNA damage for in vivo imaging, Pt drug accumulation and resultant DNA damage could be monitored in individual tumor cells, at subcellular resolution, and in real time in a live animal model of cancer. These derivatives represent promising imaging tools that will be useful in understanding further the distribution and interactions of platinum within tumors.
authors: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114 (USA).
authors: Miles A
authors: MA
authors: Miller
authors: Bjorn
authors: B
authors: Askevold
authors: Katherine S
authors: KS
authors: Yang
authors: Rainer H
authors: RH
authors: Kohler
authors: Ralph
authors: R
authors: Weissleder
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D010984:Platinum / Q000737:chemistry*; D011859:Radiography; D014183:Transplantation, Heterologous
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000970:Antineoplastic Agents; D001896:Boron Compounds; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D010984:Platinum
keywords: DNA damage; fluorescent probes; intravital imaging agents; pharmacokinetics; pharmacology