Experimemtal And Clinical Study For Evaluating Radiotherapy Effect In Patients With Brain Tumor Using ～(99m)Tc-HL91 Hypoxia Imaging

Objective:To observe the changes of ^99mTc-HL91 imaging in transplant tumors on mice before and after radiotherapy,and to investigate its mechanism of pathology which may provide a scientific evidence for evaluating the curative effect with ^99mTc-HL91 immaging during radiotherapy. Methods: 1.15 tranplant tumor mice models of H22 liver carcinoma were established. 15 model mice were divided into 3 groups. Group A was a contrast group including 5 model mice which the radiotherapy had never been used;Group B, including 5 model mice , was treated by 6 MeV electron beam from linery accelerator with a total dose of 25Gy and ^99mTc-HL91 imaging was immediately performed after the radiotherapy;Group C, including 5 model mice, was treated by 6 MeV electron beam from linery accelerator with a total dose of 25Gy and ⁹⁹Tc^m-HL91 imaging was performed 48h later after the radiotherapy.2. ^99mTc-HL91 of 1mci/0.1ml was injected into the tail vein of each mouse in Group B and C and the imaging was started two hours after injection. The ROI was used and the ratio between of tumor counts/sec and brain counts/sec(T/N) was calculated. 3.The model mice of Group A,B and C were killed and the proportion of apotosis cell and the cell proportions of G1-phase and S-phase were analised by flow cytometry. The pathology change of tumor was observed by microscope. Results: 1. The average T/N before and after radiotherapy is 2.22±0.63 and 3.11±0.90 respectively (P<0.05). The T/N was higher significantly after radiotherapy than that of before radiotherapy in group B. The average T/N before and after radiotherapy is 2.14±0.68 and 0.97±0.42 in group C respectively (P<0.05). The T/N was lower after radiotherapy than that of before radiotherapy in group C.2.The average fraction of apotosis cell in group A, B and C were 14.71%±3.04%, 24.90%±1.66%, 39.18%±7.36% respectively (P<0.05, A0.05).The fraction of G1-phase cell in group C were significently higher than that of in group A or B after radiotherapy (P<0.05).The fraction of S-phase cell in group C was significently lower after radiotherapy than that of in group A or B(P<0.05). There were some apotosis cells and a lot of cell fragments in tumor tissue after radiotherapy in group C, but there are no any inflammatory cells invading. Conclusion: 1. The ^99mTc-HL91 imaging was performed as soon as the radiotherapy ended, the concentration of ^99mTc-HL91 in tumors were significantly higher than those of before radiotherapy. The result indicated if ^99mTc-HL91 imaging was performed as soon as radiotherapy ended, the concentration of ^99mTc-HL91 in tumors would rise. 2. The ^99mTc-HL91 imaging was performed 48 hours later after the radiotherapy using , the concentrations of ^99mTc-HL91 in tumors were significantly lower than that of before radiotherapy .This result was related to the growth restrain and necrosis of tumor cells caused by radiotherapy.3.The main reason about the change of ^99mTc-HL91 hypoxia imaging was the change of oxygen pressure in the process of radiotherapy.4. ^99mTc-HL91 hypoxia imaging may be a useful method for evaluating the curative effect during radiotherapy. Objective: The purpose of this study was to evaluate the curative effect of brain tumors during radiotherapy using ^99mTc-HL91 SPECT. Methods: 1. 22 patients with brain tumors who were treated by radiotherapy with ⁶⁰Co γ -ray or 6MV X-ray in our hospital. 20 patients with brain tumors were studied at last. Those patients included 1 patient with glioma , 1 patient with medulloblastoma in cerebellum, 13 patients with brain metastasis from lung cancer(8 small cell carcinoma, 4 adenocarcinoma, 1 squamous cell carcinama), 5 patients with brain metastasis from breast cancer(4 invasive ductal carcinoma, 1 medullary carcinama). were studied. KPS grade was the criterion of evaluating symptoms.2. Both ^99mTc-HL91 SPECT and MRI were performed before, during (2 weeks after radiotherapy, dose of radiotherapy is 20 Gy) and after radiotherapy. 3.The tumor size was calculated and compaired between ^99mTc-HL91 SPECT and MRI in 20 patients. 4. KPS grade ,tumor size on ^99mTc-HL91 SPECT, MRI, and ratio of T/N (tumor counts/sec over normal brain tissue counts/sec) were observed before, during and after radiotherapy.5.The rates of symptoms improvement and the rate of imaging remission based on the brain tumor size on ^99mTc-HL91 SPECT ,MRI and T/N were evaluated during and after radiotherapy. The agreement rate between imaging remission and sympotoms improvement were evaluated. Result: 1 .The average tumor size on ^99mTc-HL91 SPECT and MRI were 11.34 ±5.88cm² and 9.46 ± 5.66 cm² respectively(P<0.05). 2. The average KPS grade before ,during and after radiotherapy were 39±13.8 57±13.8 74.5 ± 16.38 respectively/There were significance differences between 3 groups(P<0.05). The average tumor size on ^99mTc-HL91 SPECT before, during and after radiotherapy were 11.34± 5.88cm² 6.51±4.47cm² 1.95 ±3.25cm² respectively. There were significance difference between 3 groups(P<0.05). The average ratios of T/N before, during and after radiotherapy were 6.82± 1.72 5.19±1.68 1.81 ± 1.46 respectively. There were significance differencess between 3 groups (P<0.05). The tumor size on MRI imaging were 9.46 ±5.66cm² 8.52±4.63cm² 8.17 ± 4.48cm² respectively. There were no significance differences betwween 3 groups(P>0.05). 3. The rate of sympotoms improvement was 80% during radiotherapy. The rates of imaging remission based on the brain tumor size on ^99mTc-HL91 SPECT, MRI and T/N were 75%,15%,80% repectively during radiotherapy. The agreement rate between imaging remission and sympotoms improvement were 70%(tumor size on SPECT), 40% (tumor size on MRI), 65%(T/N) repectively during radiotherapy. The rate of sympotoms improvement was 100% after radiotherapy. The rates of imaging remission based on the brain tumor sizes on ^99mTc-HL91 SPECT, MRI and T/N were 100%, 25%,. 95% repectively after radiotherapy. The agreement rate between imaging remission and sympotoms improvement were 100%(tumor size on SPECT), 25%(tumor size on MRI), 95%(T/N) repectively. Conclusion: 1. ^99mTc-HL91 SPECT was a valuable tool for evaluating the early effect of brain tumor in process of radiotherapy.2.The average tumor size on ^99mTc-HL91 SPECT was not accordance with that on MRI,this result may help clinician make radiotherapy programe.3.The ratio of T/N was not a feasible method in evaluation the curative effect during radiotherapy.