title: Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.
abstract: Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Chris Jun Hui
authors.initials: CJ
authors.lastname: Ho
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Ghayathri
authors.initials: G
authors.lastname: Balasundaram
authors.affiliation: 1] Institute for Biological and Medical Imaging, Helmholtz Center Munich, Germany [2] iThera Medical, GmbH, Germany.
authors.forename: Wouter
authors.initials: W
authors.lastname: Driessen
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Ross
authors.initials: R
authors.lastname: McLaren
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Chi Lok
authors.initials: CL
authors.lastname: Wong
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: U S
authors.initials: US
authors.lastname: Dinish
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Amalina Binte Ebrahim
authors.initials: AB
authors.lastname: Attia
authors.affiliation: 1] Institute for Biological and Medical Imaging, Helmholtz Center Munich, Germany [2] Technical University of Munich, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: 1] Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore [2] School of Physics, National University of Ireland, Galway, Ireland.
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
mesh_terms: D045744:Cell Line, Tumor; D002735:Chlorophyllides; D003287:Contrast Media / Q000493:pharmacokinetics; D003503:Cyclobutanes / Q000493:pharmacokinetics / Q000627:therapeutic use; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D054833:Isoindoles; D061986:MCF-7 Cells; D008751:Methylene Blue / Q000493:pharmacokinetics / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D010636:Phenols / Q000493:pharmacokinetics / Q000627:therapeutic use; D061088:Photoacoustic Techniques / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use; D011524:Protoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D017967:Zinc Compounds
chemical_list: D002735:Chlorophyllides; D003287:Contrast Media; D003503:Cyclobutanes; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D010636:Phenols; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D017967:Zinc Compounds; C480596:squaraine; C052159:Zn(II)-phthalocyanine; C062985:phytochlorin; C028025:protoporphyrin IX; D008751:Methylene Blue