| Purpose To investigate the effects of animal preparation on the mieroPET imaging in nude mouse tumor xenografts and optimize imaging protocol. Methods Thirty-six nude mice implanted with human epidermoid carcinoma cell lines A431were randomly divided into6groups. Group A:no fasting, room temperature (20～22℃), no anesthesia (duration on FDG biodistribution), FDG given by intravenous injection; Group B:fasting (6-8h), warming (30～32℃), anesthesia (duration on FDG biodistribution), FDG given by intravenous injection; Group C:no fasting, warming, anesthesia, FDG given by intravenous injection; Group D:fasting, room temperature, anesthesia, FDG given by intravenous injection; Group E:fasting, warming, no anesthesia, FDG given by intravenous injection; Group F:fasting, warming, anesthesia, FDG given by intraperitoneal injection. Serum glucose level were measured before FDG injection.%ID/gmax of subcutaneous tumor, neck muscle, brown adipose tissue, brain, liver, kidney, myocardium, harderian gland and intestine of group A-F were measured after scanning.%ID/gmax of subcutaneous tumor of group B and group F were measured after the second scanning. Results (1) Tumor FDG uptake significantly correlated with glycemia in group B, group C and group F (P<0.05). No significant correlation was found between tumor FDG uptake and glycemia in groupA, group D and group E, respectively (P>0.05).(2) Brown adipose tissue FDG uptake was8.03±1.29in group A. Muscle FDG uptake was16.07±5.20in group A. FDG uptake of brown adipose tissue and muscle decreased71.98%and81.84%, respectively, in group B than group A (P <0.05). In different groups, uptake by brain, liver, kidney, myocardium and harderian gland were not significantly difference (P>0.05, for all).(3) Uptake of tumor-to-organ ratio was lowest in group A. Uptake of the tumor-to-muscle, the tumor-to-liver and the tumor-to-brown fat ratios increased6.5-fold,1.29-fold and4.76-fold, respectively, in group B than group A (P<0.05. for all). Under the study conditions of group B, the imaging contrast of tumor was improved.(4) No significant differences were found for tumor FDG uptake by different method of injection in the first scanning (P=0.364). After the second scanning, FDG were gathered in abdominal cavity by intraperitoneal injection which lead to low uptake of tumor and normal tissue. Significant differences were found for tumor FDG uptake by intraperitoneal injection between the first scanning and the second scanning (P=0.025).(5) High uptake by intestine was66.67%and45.83%in non-fasting and fasting, respectively. Conclusion Animal preparation has a significant effect on the FDG biodistribution in normal tissues and the uptake in subcutaneous tumor. The fasting, warming, anesthesia, intravenous injection could improve imaging quality and reproducibility. Purpose To investigate whether FDG microPET-CT can be used to monitor tumor metabolic response to gefitinib in nude mouse tumor xenografts. Methods Sixteen nude mice implanted with human epidermoid carcinoma cell lines A431were randomly divided into a treatment group (n=10) and a control group (n=6). Ten nude mice implanted with human lung adenocarcinoma cell lines A549were randomly divided into a treatment group (n=5) and a control group (n=5). FDG microPET imaging was used to assess tumor metabolic activity. Imaging was done before (day0) and at days2,7, and14after the intragastric administration of gefitinib (100mg/kg, once a day) or sterile water. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor and acquire the maximum percentage injected dose per gram (%ID/gmax). The microCT was used to measure the tumor volume. According to the tumor volume at the14th day, tumors were categorized into a sensitive group, an insensitive group and a resistant group to gefitinb. If tumor volume decreased, it was considered as sensitive. If tumor volume increased slowly, which was smaller than the control group, it was considered as insensitive (P<0.05). If the tumor volume increased more rapidly, which was not significantly different between the treatment group and the control group, it was considered as resistant (P>0.05). Then, the pathologic changes of tumor after gefitinib therapy were analyzed. Results (1) On day2, the average changes of A431tumor FDG uptake were (-30.92±6.66)%,(-5.68±6.95)%and (7.72±3.85)%in the sensitive group, the insensitive group and the control group respectively (P<0.05, for all). On day2, no significant differences in the size of tumor were found between the sensitive group and the insensitive group (P=0.169). On day7, the size of tumor was significantly different between the sensitive group and the insensitive group (P=0.034). On day14, neerotic fractions were markedly seen in the sensitive group. Tumor neerotic ratios were between the sensitive, insensitive and control groups (P<0.05, for all).(2) The A549tumor FDG uptake, volume and neerotic fractions were not significantly different between the treatment group and the control group on days0,2,7and14(P>0.05, for all).(3) The AUC of Δ%ID/gmax all was1.000in Day2, Day7and Day14(P=0.011for all). After2days of gefitinib treatment for A431tumor, when a cutoff value of-16%in A%ID/gmax for prediction of tumor response to gefitinib, the sensitiviy and the specificity both were100%. Conclusion (1) On day2, the changes of A431tumor FDG uptake were significantly different between the sensitive group and the insensitive group. On day7, the size of tumor was significantly different between the sensitive group and the insensitive group. On day14, significant necrotic fractions were seen in the sensitive group.(2) The A549tumor FDG uptake, volume and necrotic fractions were not significantly different between the treatment group and the control group on days0,2,7and14.(3) The changes of tumor FDG uptake in Day2, Day7and Day14can be used to monitor the response to gefitinib in A431tumor.(4) On day2, a cutoff value of-16%in A%ID/gmax has high sensitiviy and specificity for prediction of tumor response to gefitinib. Purpose This study was to investigate whether changes in FDG uptake after gefitinib treatment correlated with changes in P-EGFR, Ki-67, Glut-1and caspase-3expressions and assess the feasibility of using microPET-CT to monitor the early response to gefitinib in vivo. Methods Forty-eight nude mice implanted with human epidermoid carcinoma cell lines A431were randomly divided into a treatment group (n=24) and a control group (n=24). FDG microPET imaging was used to assess tumor metabolic activity. Imaging was done before and at days2,7, and14after the intragastric administration of gefitinib (100mg/kg, once a day) for the treatment group or sterile water for the control group. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor and acquire the maximum percentage injected dose per gram (%ID/gmax). According to the change of tumor FDG uptake on day2, tumors were categorized into a sensitive group and an insensitive group. If tumor uptake decreased≥16%, it was considered as sensitive tumor. If tumor uptake decreased<16%, it was considered as insensitive tumor. Then, the tumor FDG uptake and the immunohistochemistry results of P-EGFR, Ki-67, Glut-1and caspase-3before and after gefitinib therapy were analyzed. Results (1) After gefitinib therapy, the FDG uptake of tumor decreased. On day2, Δ%ID/gmax was (-31.07±6.33)%,(-6.14±5.31)%and (4.18±3.81)%in the sensitive group, the insensitive group and the control group, respectively. Significant differences in Δ%ID/gmax were found between the sensitive, insensitive and control groups at days2,7and14after gefitinib treament (P<0.05, for all).(2) After gefitinib therapy, P-EGFR expressions of tumor decreased. On day2, AP-EGFR was (-89.20±4.10)%,(-84.94±3.40)%and (-5.56±35.10)%in the sensitive group, the insensitive group and the control group, respectively. Significant differences in AP-EGFR were found between the control group and the sensitive or insensitive groups at day2after gefitinib treatment (P<0.01, for both). No significant differences in AP-EGFR were found between the sensitive and insensitive groups (P=0.811).(3) After gefitinib therapy, Ki-67expressions of tumor decreased. On day2, AKi-67was (-79.02±5.51)%,(-50.14±10.73)%and (32.95±19.39)%in the sensitive group, the insensitive group and the control group, respectively. Significant differences in AKi-67were found between the sensitive, insensitive and control groups at days2,7and14after gefitinib treatment (P<0.05, for all).(4) After gefitinib therapy, Glut-1expressions of tumor decreased. On day2, ΔGlut-1was (-47.70 ±9.75)%,(-20.47±6.15)%and (8.79±12.86)%in the sensitive group, the insensitive group and the control group, respectively. Significant differences in AGlut-1were found between the sensitive, insensitive and control groups at days2,7and14after gefitinib treatment (P<0.05, for all).(5) After gefitinib therapy, caspase-3expressions of tumor increased. On day2, Acaspase-3was (62.71±9.71)%,(55.81±12.35)%and (4.93±6.93)%in the sensitive group, the insensitive group and the control group, respectively. Significant differences in Acaspase-3were found between the control group and the sensitive or insensitive groups at day2after gefitinib treatment (P<0.01, for both). No significant differences in Acaspase-3were found between the sensitive and insensitive groups (P=0.325).(6)%ID/gmax significantly correlated with Ki-67expressions and Glut-1expressions at days0,2,7and14(P<0.05, for all).(7) A%ID/gmax significantly correlated with ΔKi-67and AGlut-1at days2,7and14after gefitinib treatment (P<0.05, for all). Conclusion After gefitinib therapy, the sensitive tumor FDG uptake are markedly lower than the insensitive tumor. After gefitinib therapy, Ki-67and Glut-1expressions of the sensitive tumor are markedly lower than the insensitive tumor. The changes of tumor FDG uptake closely correlate with the changes of Ki-67and Glut-1expressions associated with gefitinib therapy in the murine cancer models. On day2, according to the tumor uptake decrease rate with gefitinib administration, the sensitive tumors could be early detected in vivo.
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