Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy.
A new type of monoclonal antibody (mAb)-based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a near-infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, target-selective necrotic cell death. However, tumor shrinkage takes several days to occur, making it difficult to detect earlier changes in the tumor. In this study, Panitumumab targeting the epidermal growth factor receptor (EGFR1) conjugated to IR700 was used to treat EGFR-expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100 J cm(-2)) in xenograft tumors in mice. Indocyanine green (ICG) dynamic imaging was evaluated for monitoring cytotoxic effects for the first hour after PIT. Our results demonstrated a statistical difference (p < 0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50 J cm(-2): 2.94 ± 0.35 vs 5.22 ± 0.92, p = 0.02; and 100 J cm(-2) : 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) as early as 20 min post ICG injection. However, no significant difference (p > 0.05) in ICG intensity between control and PIT treated tumors was evident in the lower light exposure group at any time points up to 60 min (10 J cm(-2) : 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; and 30 J cm(-2): 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07). Similarly, the retention index (background to corrected uptake ratio of ICG) varied with light exposure. In conclusion, ICG may serve as a potential indicator of acute cytotoxic effects of mAb-IR700-induced PIT even before morphological changes can be seen in targeted tumors.
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892-1088, USA.
Towhid
T
Ali
Takahito
T
Nakajima
Kohei
K
Sano
Kazuhide
K
Sato
Peter L
PL
Choyke
Hisataka
H
Kobayashi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005456:Fluorescent Dyes; D006801:Humans; D007167:Immunotherapy; D007208:Indocyanine Green; D051379:Mice; D000077544:Panitumumab; D010789:Phototherapy
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D007208:Indocyanine Green
cancer fluorescence imaging; indocyanine green; photoimmunothearpy; super-enhanced permeability and retention effect