Fluorescence detection of camptothecin anticancer drugs by two-photon excitation

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

Research output: Contribution to journalConference article

2 Scopus citations

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 μM and 46 μM 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 ns, 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 μM and 1 μM 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.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalProceedings of SPIE - The International Society for Optical Engineering
Volume3259
DOIs
StatePublished - 1 Dec 1998
EventSystems and Technologies for Clinical Diagnostics and Drug Discovery - San Jose, CA, United States
Duration: 26 Jan 199827 Jan 1998

Keywords

  • Camptothecin
  • Cross-section
  • Fluorescence
  • Near infrared
  • Time-resolved
  • Topoisomerase I
  • Topotecan
  • Two-photon excitation

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