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Proceedings Paper

Fluorescence detection of camptothecin anticancer drugs by two-photon excitation
Author(s): Thomas G. Burke; Magda Malak; David Bom; Dennis P. Curran; Henryk M. Malak; Ignacy Gryczynski; Joseph R. Lakowicz
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Paper 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.

Paper Details

Date Published: 10 April 1998
PDF: 8 pages
Proc. SPIE 3259, Systems and Technologies for Clinical Diagnostics and Drug Discovery, (10 April 1998); doi: 10.1117/12.307334
Show Author Affiliations
Thomas G. Burke, Univ. of Kentucky College of Pharmacy and Markey Cancer Ctr. (United States)
Magda Malak, Univ. of Maryland School of Medicine/Baltimore (United States)
David Bom, Univ. of Pittsburgh (United States)
Dennis P. Curran, Univ. of Pittsburgh (United States)
Henryk M. Malak, Univ. of Maryland School of Medicine/Baltimore (United States)
Ignacy Gryczynski, Univ. of Maryland School of Medicine/Baltimore (United States)
Joseph R. Lakowicz, Univ. of Maryland School of Medicine/Baltimore (United States)


Published in SPIE Proceedings Vol. 3259:
Systems and Technologies for Clinical Diagnostics and Drug Discovery
Gerald E. Cohn; John C. Owicki, Editor(s)

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