Thymidine analogues to assess microperfusion in human tumors.
OBJECTIVE
To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342.


METHODS
Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored.


RESULTS
We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r = 85, p = 0.0004), despite some mismatches on a per-vessel basis.


CONCLUSIONS
Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.
Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Hilde L
HL
Janssen
Anna S
AS
Ljungkvist
Paul F
PF
Rijken
Debbie
D
Sprong
Jan
J
Bussink
Albert J
AJ
van der Kogel
Karin M
KM
Haustermans
Adrian C
AC
Begg
D000818:Animals; D001562:Benzimidazoles / Q000032:analysis; D001973:Bromodeoxyuridine / Q000032:analysis*; D005456:Fluorescent Dyes / Q000032:analysis*; D006801:Humans; D007065:Idoxuridine / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply*; D014183:Transplantation, Heterologous
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D001973:Bromodeoxyuridine; D007065:Idoxuridine; C017807:bisbenzimide ethoxide trihydrochloride