Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe

Thommey P. Thomas; Jing Yong Ye; Chu-Sheng Yang; Monthiri Myaing; Istvan J. Majoros; Alina Kotlyar; Zhengyi Cao; Theodore B. Norris; James R. Baker Jr.

doi:10.1117/12.645084

28 February 2006 Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe

Thommey P. Thomas, Jing Yong Ye, Chu-Sheng Yang, Monthiri Myaing, Istvan J. Majoros, Alina Kotlyar, Zhengyi Cao, Theodore B. Norris, James R. Baker Jr.

Author Affiliations +

Proceedings Volume 6095, Nanobiophotonics and Biomedical Applications III; 60950Q (2006) https://doi.org/10.1117/12.645084
Event: SPIE BiOS, 2006, San Jose, California, United States

Abstract

Real-time fluorescence measurement in deep tumors in live animals (or humans) by conventional methods has significant challenges. We have developed a two-photon optical fiber fluorescence (TPOFF) probe as a minimally invasive technique for quantifying fluorescence in solid tumors in live mice. Here we demonstrate TPOFF for real-time measurements of targeted drug delivery dynamics to tumors in live mice. 50-femtosecond laser pulses at 800 nm were coupled into a single mode optical fiber and delivered into the tumor through a 27-gauge needle. Fluorescence was collected back through the same fiber, filtered, and detected with photon counting. Biocompatible dendrimer-based nanoparticles were used for targeted delivery of fluorescent materials into tumors. Dendrimers with targeting agent folic acid and fluorescent reporter 6-TAMRA (G5-6T-FA) were synthesized. KB cell tumors expressing high levels of FA receptors were developed in SCID mice. We initially demonstrated the specific uptake of the targeted conjugates into tumor, kidney and liver, using the TPOFF probe. The tumor fluorescence was then taken in live mice at 30 min, 2 h and 24 h with the TPOFF probe. G5-6T-FA accumulated in the tumor with maximum mean levels reaching 673 ± 67 nM at the 2 h time point. In contrast, the levels of a control, non-targeted conjugate (G5-6T) at 2 h reached a level of only 136 ± 28 nM in tumors, and decrease quickly. This indicates that the TPOFF probe can be used as a minimally invasive detection system for quantifying the specific targeting of a fluorescent nanodevice on a real-time basis.

Citation Download Citation

Thommey P. Thomas, Jing Yong Ye, Chu-Sheng Yang, Monthiri Myaing, Istvan J. Majoros, Alina Kotlyar, Zhengyi Cao, Theodore B. Norris, and James R. Baker Jr. "Tissue distribution and real-time fluorescence measurement of a tumor-targeted nanodevice by a two photon optical fiber fluorescence probe", Proc. SPIE 6095, Nanobiophotonics and Biomedical Applications III, 60950Q (28 February 2006); https://doi.org/10.1117/12.645084

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