title: MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy.
abstract: Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT. A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor. One day later, only right sided tumor was exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using gadofosveset for six mice and gadopentetate dimeglumine for another six mice. T2 relaxation times, the apparent diffusion coefficient (ADC) for the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm2 and enhancement indices were compared before and after NIR-PIT using a two-sided paired t-test. For treated tumors, T2 relaxation time increased after NIR-PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02). In conclusion, prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Research Technology Program, SAIC-Frederick Inc., National Cancer Institute, Bethesda, MD, USA.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods*; D007259:Infrared Rays; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000628:therapy*; D009942:Organometallic Compounds / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D018796:Immunoconjugates; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D005682:Gadolinium; D019786:Gadolinium DTPA; C109932:gadofosveset trisodium
keywords: MRI; T2 relaxation time; diffusion weighted image; gadofosveset; near infrared photoimmunotherapy