Intratumoral pharmacokinetic analysis by 19F-magnetic resonance spectroscopy and cytostatic in vivo activity of gemcitabine (dFdC) in two small cell lung cancer xenografts.
BACKGROUND
Gemcitabine, 2'2'difluoro-deoxycytidine (dFdC), has shown activity in several preclinical models, and presently the compound is being clinically evaluated in patients with lung cancer and other solid tumors.


METHODS
The cytostatic in vivo activity of dFdC was tested in the two human small cell lung cancer (SCLC) tumor xenografts CPH SCCL 54A and 54B in nude mice. Non-invasive monitoring of the uptake and elimination of fluorine in the individual tumors was performed by in vivo 19F-magnetic resonance spectroscopy, using a 2.9 T magnet. Five dose levels in the range 5-80 mg/kg i.p. every third day, four times were applied.


CONCLUSIONS
Significant activity of gemcitabine was demonstrated in both SCLC tumor lines. The tumor line 54A is the most sensitive to radiotherapy, doxorubicin, and nitrosoureas; but in this case the 54B tumors were more sensitive to gemcitabine therapy than 54A. This difference in sensitivity seems to be related to different delivery or uptake of the compound in the two tumor lines, since the 19F-MRS demonstrated a significantly higher antitumor accumulation of fluorine in 54B tumors compared with 54A (p < 0.05, Wilcoxons 2-sided test) following the same single dose of the drug.
Kristjansen
P E
PE
Department of Oncology, Finsen Institute-Rigshospitalet, University of Copenhagen, Denmark.
Quistorff
B
B
Spang-Thomsen
M
M
Hansen
H H
HH
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005461:Fluorine; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005461:Fluorine; D000093542:Gemcitabine