Fluorescence detection of camptothecin anticancer drugs by two-photon excitation

Thomas G. Burke; Magda Malak; David Bom; Dennis P. Curran; Henryk M. Malak; Ignacy Gryczynski; Joseph R. Lakowicz

doi:10.1117/12.307334

10 April 1998 Fluorescence detection of camptothecin anticancer drugs by two-photon excitation

Thomas G. Burke, Magda Malak, David Bom, Dennis P. Curran, Henryk M. Malak, Ignacy Gryczynski, Joseph R. Lakowicz

Proceedings Volume 3259, Systems and Technologies for Clinical Diagnostics and Drug Discovery; (1998) https://doi.org/10.1117/12.307334
Event: BiOS '98 International Biomedical Optics Symposium, 1998, San Jose, CA, United States

Abstract

Hycamtin is a camptothecin anticancer analogue containing a dimethylaminomethyl substituent at position 9 and a hydroxy functionality at position 10. Using an excitation wavelength of 800 nm we have compared the two-photon cross sections and excited-state lifetimes from several camptothecins in phosphate buffered saline solution with and without the presence of human serum albumin (HSA). Drug and HSA concentrations of 10 (mu) M and 46 (mu) M were employed in our studies. In phosphate buffered saline solution containing HSA the following excited-state lifetimes (ns) and two- photon cross-sections (10^-50 cm⁴ s/photon), respectively, were determined: hycamtin (4.3 nm, 36); camptothecin (1.3 ns, 1); 7-t-butyldimethylsilyl-10- hydroxycamptothecin (1.7 ns, 3.7); 7-t-butyldimethylsilyl- camptothecin (1.9 ns, 1.9); 7-trimethylsilyl-10- aminocamptothecin (6.3 ns; 35); and 7-trimethylsilyl-10- hydroxycamptothecin (1.8 ns; 2.2). Our results indicate that Hycamtin exhibits a high cross-section relative to the parent camptothecin molecule and represents one of the best camptothecin analogues to detect using two-photon excitation. Hycamtin was detected at concentrations as low as 0.05 (mu) M and 1 (mu) M in plasma and whole blood, respectively. The newly synthesized analogue 7- trimethylsilyl-10-aminocamptothecin was found to display similar lifetime and two-photon cross section values relative to Hycamtin. Thus, fluorescence detection with two- photon excitation may prove to be of advantage in the development of this promising new experimental therapeutic.

Citation Download Citation

Thomas G. Burke, Magda Malak, David Bom, Dennis P. Curran, Henryk M. Malak, Ignacy Gryczynski, and Joseph R. Lakowicz "Fluorescence detection of camptothecin anticancer drugs by two-photon excitation", Proc. SPIE 3259, Systems and Technologies for Clinical Diagnostics and Drug Discovery, (10 April 1998); https://doi.org/10.1117/12.307334

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