To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.
Summary The cellular distribution of 4-borono-2-["8F]fluoro-L-phenylalanine (['8F]FBPA, an analog of pboronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P <0.05), the slowest being in FM3A (P<0.001). p-Boronophenylalanine (BPA) has been studied as a potential agent for boron neutron capture therapy (BNCT) for melanomas (Mishima et al., 1989a,b). The success of this treatment is dependent on the highly selective localisation and concentration of boron-10 in tumours vs normal tissues. Biodistribution studies and radiation dosimetry based on pharmacokinetics have indicated that BPA acts as a biochemically targeted boron carrier for melanomas in vivo (Barth et al., 1990;Coderre et al., 1988). Double-labelled neutron capture radiograms of '°B-L-BPA and [3H]Thd autoradiograms from the same whole-body section showed that high concentration of boron in the tumour corresponded closely with areas of rapid cell division (Coderre et al., 1987). However, the relationship of BPA accumulation to DNA synthesis and pigmentation is still unclear (Tsuji et al., 1983;Ichihashi et al., 1982;Ishiwata et al., 1992a).In recent studies carried out to accurately determine the in vivo concentration of the compound, '8F labelled borono-FBPA) has been synthesised as a positron emitting tracer which can be quantified non-invasively in vivo by positron emission tomography (PET) (Ishiwata et al., 1991a,b; 1992a,b). Chemically determined '0B-BPA concentration in the Greene's melanomas was comparable to the value estimated with ['8F]FBPA (Yamada et al., 1990).Under a safety light, frozen 5-.m sections were directly mounted on slides coated with NTB2 emulsion. After 4 h of exposure under dry ice cold, the sections were fixed with 5% acetic acid; the autoradiograms were developed in Konidol-X (Konica, Japan), fixed in Kodak general purpose fixer (Kodak, Japan), washed, and dried. Three days after the first ARG for the complete decay of '8F (t1/2= 109.8 min), the second ARG was processed with ET2F stripping film. Under a safety light, the slides with sections and the first autoradiogram were covered with ET2F stripping film; the film-
We carried out a study to evaluate treatment response and residual mass in lung cancer with positron emission tomography (PET), using L-[methyl-11C]methionine (MET). MET tumour uptake and tumour volume measured by computed tomography (CT) before and within 2 weeks after radiotherapy or chemoradiotherapy were compared in 43 studies of 21 patients. Ten patients with local control (no recurrence) of tumour showed a larger decrease in MET uptake (65.2% +/- 12.2%) than in tumour volume (50.8% +/- 9.6%, P < 0.01). Five patients with early recurrence (from 1 to 4 months) showed smaller decreases in both MET uptake (22.2% +/- 13.5%) and tumour volume (28.6% +/- 20.0%) than those in the no-recurrence group (P < 0.01). Four patients with late recurrence (after 11 months or more) showed a similar decrease to the no-recurrence group in MET uptake (72.8% +/- 14.8%) but little change in tumour volume (18.5% +/- 19.0%), the latter result corresponding to that in the early-recurrence group. Using tumour volume only, the no-recurrence group was differentiated from both the early- and the late-recurrence group (P < 0.01), but the early-recurrence group was not differentiated from the late-recurrence group. Using the MET uptake data, the early-recurrence group was clearly distinguished from the late-recurrence group (P < 0.01), but the late-recurrence group was indistinguishable from the no-recurrence group. CT was useful in distinguishing the no-recurrence group from the groups in which there was ultimate recurrence, whether early or late. When a residual mass is seen on CT, PET seems to be helpful in evaluating tumour viability.
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