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Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy
- Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy
- Cheruku, Ravindra R.; Cacaccio, Joseph; Durrani, Farukh A.; Tabaczynski, Walter A.; Watson, Ramona; Marko, Aimee; Kumar, Rahul; El-Khouly, Mohamed E.; Fukuzumi, Shunichi; Missert, Joseph R.; Yao, Rutao; Sajjad, Munawwar; Chandra, Dhyan; Guru, Khurshid; Pandey, Ravindra K.
- Ewha Authors
- Shunichi Fukuzumi
- SCOPUS Author ID
- Shunichi Fukuzumi
- Issue Date
- Journal Title
- JOURNAL OF MEDICINAL CHEMISTRY
- JOURNAL OF MEDICINAL CHEMISTRY vol. 62, no. 5, pp. 2598 - 2617
- AMER CHEMICAL SOC
- SCI; SCIE; SCOPUS
- Document Type
- The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to F-18-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (I-124-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 mu Ci/mouse.
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