Mesoscopic fluorescence tomography of a photosensitizer (HPPH) 3D biodistribution in skin cancer.
OBJECTIVE
Photodynamic therapy (PDT) is a promising strategy for treating cancer. PDT involves three components: a photosensitizer (PS) drug, a specific wavelength of drug-activating light, and oxygen. A challenge in PDT is the unknown biodistribution of the PS in the target tissue. In this preliminary study, we report the development of a new approach to image in three dimensions the PS biodistribution in a noninvasive and fast manner.


METHODS
A mesoscopic fluorescence tomography imaging platform was used to image noninvasively the biodistribution of 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH) in preclinical skin cancer models. Seven tumors were imaged and optical reconstructions were compared to nonconcurrent ultrasound data.


RESULTS
Successful imaging of the HPPH biodistribution was achieved on seven skin cancer tumors in preclinical models with a typical acquisition time of 1 minute. Two-dimensional fluorescence signals and estimated three-dimensional PS distributions were located within the lesions. However, HPPH distribution was highly heterogeneous with the tumors. Moreover, HPPH distribution volume and tumor volume as estimated by ultrasound did not match.


CONCLUSIONS
The results of this proof-of-concept study demonstrate the potential of MFMT to image rapidly the HPPH three-dimensional biodistribution in skin cancers. In addition, these preliminary data indicate that the PS biodistribution in skin cancer tumors is heterogeneous and does not match anatomical data. Mesoscopic fluorescence molecular tomography, by imaging fluorescence signals over large areas with high spatial sampling and at fast acquisition speeds, may be a new imaging modality of choice for planning and optimizing of PDT treatment.
Biomedical Engineering Department, Rensselaer Polytechnic Institute, 110 8th St, JEC 7036, Troy, NY 12180.
Mehmet S
MS
Ozturk
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY.
Daniel
D
Rohrbach
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY.
Ulas
U
Sunar
Biomedical Engineering Department, Rensselaer Polytechnic Institute, 110 8th St, JEC 7036, Troy, NY 12180. Electronic address: intesx@rpi.edu.
Xavier
X
Intes
D000287:Administration, Topical; D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D046169:Dermoscopy / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014018:Tissue Distribution; D041622:Tomography, Optical / Q000379:methods
D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a
3D biodistribution; fluorescence tomography; photosensitizer; ultrasound