Tm. Sitnik et Bw. Henderson, THE EFFECT OF FLUENCE RATE ON TUMOR AND NORMAL TISSUE RESPONSES TO PHOTODYNAMIC THERAPY, Photochemistry and photobiology, 67(4), 1998, pp. 462-466
Photodynamic therapy (PDT), carried out at low fluence rates, may enha
nce tumor response as well as affect treatment selectivity. We have st
udied the effects of fluence rate on the response of the murine radiat
ion-induced fibrosarcoma (RIF) to PDT using Photofrin(R) (5 mg/kg), Tu
mor response was tested over a large range of fluence rates (10-200 mW
/cm(2)) and fluences (25-378 J/ cm(2)), Low fluence rates were more ef
ficient; similar to 60 J/cm(2) at 10 mW/cm(2) was needed to achieve th
e same tumor growth delay as similar to 100 J/cm(2) at 150 mW/cm(2) an
d similar to 150 J/cm(2) at 200 mW/cm(2). Despite this increased effic
iency, lower fluence rates still required longer treatment times for e
quivalent anti-tumor effects: 95 min for 57 J/cm(2) at 10 mW/cm(2) ver
sus 11 min for 100 J/cm(2) at 150 mW/cm(2). Effects of fluence rate on
the PDT toxicity to normal tissue were examined through the response
of the murine (C3H) foot to Photofrin(R) PDT, Treatment with condition
s that produced equivalent tumor responses, i,e, 57 J/cm(2) at 10 mW/c
m(2) and 100 J/cm(2) at 150 mW/cm(2), resulted in a more severe foot r
esponse at the higher fluence rate (median peak response: 0.9 at 10 mW
/cm(2), 1.5 at 150 mW/cm(2)) with more time required for tissue to ret
urn to normal (8 days at 10 mW/cm(2), at least 30 days at 150 mW/cm(2)
). However, when feet were treated with an equal fluence of 100 J/cm(2
) at various fluence rates, longer healing times accompanied the lower
fluence rate treatments. Overall, this paper demonstrates that lower
PDT fluence rates are associated with increased efficiency of tumor re
sponse. If this increased efficiency is accounted for by lowering trea
tment fluence, lower fluence rates also may result in a more favorable
normal tissue response to treatment.