Jm. Schuster et al., HYPERTHERMIC MODULATION OF RADIOLABELED ANTIBODY UPTAKE IN A HUMAN GLIOMA XENOGRAFT AND NORMAL-TISSUES, International journal of hyperthermia, 11(1), 1995, pp. 59-72
These experiments investigate the biodistribution of radiolabelled MAb
in a human glioma xenograft model after 4 h of local hyperthermia (HT
) with a twofold purpose: to maximize the ratio of cumulative isotope
activity in tumour relative to normal tissues, and to examine the temp
erature dependence of the effect. Restrained, unanaesthetized athymic
nude mice bearing 150-200 mm(3) s.c. human glioma xenografts (D-54 MG)
were given 5 mu g I-125-labelled specific and I-131-labelled non-spec
ific MAb immediately prior to HT (water bath) for 4 h. Cohorts of five
animals were killed at 0, 4, 8, 12 and 24 h after HT, and normal and
tumour tissues were analysed for activity of each isotope. MAb uptake
in tumour was greater with HT than with controls, and greater for spec
ific MAb than for non-specific MAb. Uptake in thyroid was not signific
antly affected by tumour HT, suggesting that HT does not increase the
rate of dehalogenation. Uptake in several other normal tissues away fr
om the heated site was significantly increased (as were reported previ
ously in mice anaesthetized with pentobarbital sodium during treatment
; Cope et al. 1990), but the temporal pattern was different from that
observed in tumour, suggesting that short-lived isotopes might lead to
preferential dose deposition in heated tumour. Doses to various tissu
es were calculated for isotopes having a range of half-lives; the resu
lts clearly indicated that maximum differential in uptake between tumo
ur and normal tissues would occur for isotopes with half-lives < 3 day
s. A separate series of experiments compared tumour uptake for 40, 42
and 44 degrees C HT. These results demonstrated that 42 and 44 degrees
C HT created maximum enhancement in specific antibody uptake over con
trols. Specific MAb was retained over time in 42 degrees C-heated tumo
urs, whereas significant washout occurred for non-specific MAb, which
indicates that MAb retention was due to increased specific binding at
this temperature and not vascular damage with antibody trapping. Reten
tion of both specific and nonspecific MAb was seen at 44 degrees C, su
ggesting that vascular damage becomes an important non-specific mechan
ism far antibody retention at higher temperatures.