| Breast cancer is one of the most common neoplasms which with an incidence of 2.724‰ and a mortality of 0.707‰.At the same time,women die of cancer often leading by Breast cancer.Breast cancer usually has longer course,easy to lymph nodes and bones metastasis and other characteristics.Recently,surgical operation,chemotherapy（including neo-adjuvant chemotherapy and traditional chemotherapy）,endocrine therapy,target therapy and radiotherapy are used in common.Doctors choose the methods suit for patients based on their different characteristics.But these methods cannot cover all type of Breast cancer,such as Triple-negative breast carcinoma（TNBC）,which has no effective mode to treat.Chemokine receptor 4（CXCR4）is a G-protein coupled chemokine receptor with seven trans-membrane domains.By binding its ligand CXCL12,the CXCR4 plays an important role in process of pathology and physiology.Many researchers found that CXCR4/CXCL12 is closely related to the biology characteristics of breast cancer cell.The inhibitor of CXCR4 can interrupt the growth of cancer cells.Based on this phenomenon,researchers find a new way to treat breast cancer.CXCR4 has a high expression in breast tumor,especially in the TNBC.In Chu QD’s research,more than 75% of the TNBC has a high expression of CXCR4,this characteristic gives the TNBC a new way to treat.The target tracer of CXCR4 may help doctors choose patients suit for this method before clinical,calculate the dosage,and evaluate the effective.So that,tracer without invasion is very necessary for clinical.Finding the target tracer of CXCR4 may help physicians to choose the patients suit for treating with CXCR4 inhibitor before the cycle starting,and follow-up the effect.The tracer can bring convenience to clinical.The topic of this study is to estimate the safety of 68Ga-NOTA-NFB by measuring the bio-distribution and dosimetry.Apply the tracer in breast cancer,and evaluate traits of PET/CT imaging by 68Ga-NOTA-NFB.Objectives: This study aimed to estimate the safety of 68Ga-NOTA-NFB by measuring the bio-distribution and radiation dosimetry in volunteers.At the same time,investigated the clinical characteristics of 68Ga-NOTA-NFB in breast cancer with chemokine receptor 4 by PET/CT,and the correlation with 18F-FDG and pathology.Methods: 1.The bio-distribution and dosimetry of 68Ga-NOTA-NFB in volunteers.Totally,6 healthy volunteers without cancer and inflammation join in this study.The study chooses them based on their medical history,physical examination,electrocardiogram and blood tests.68Ga-NOTA-NFB in 0.1m Ci/kg was injected to the healthy volunteers with in 30 seconds.Take the PET scans at 0,30,60,120 and 180 min after the tracer injection and draw the SUVmax-time curve.1 ml blood samples were obtained at 1,3,5,10,30,60,90,120,150 and 180 min after injecting 68Ga-NOTA-NFB.Measure the radioactivity of the whole blood.After centrifugation,using the Gamma counter measured the radioactivity in plasma.And then make the radioactivity-time curve.2.The characteristics of 68Ga-NOTA-NFB PET imaging in breast cancer.From June 2014 to December 2014,11 patients with breast cancer（all female,age range: 38-68）were recruited in this study.They took PET/CT imaging by 68Ga-NOTA-NFB and 18F-FDG.Compare the results of PET imaging in primary and lymphatic metastasis.3 patients took PET again after 4 cycles of neo-adjuvant chemotherapy and before surgery.PET/CT results were considered positive when the lesions uptake the tracer.The doctors used ROI to measure the positive lesions.T-test and correlation analysis were used for statistical analysis.Results: 1.The bio-distribution and dosimetry of 68Ga-NOTA-NFB in volunteers.The radioactivity was accumulated predominantly in the spleen and urinary bladder,followed by live,kidneys and the red marrow.The activity in the spleen decreased quickly over time（from 23.71 to 12.04）.The initial uptakes in liver（from 7.82 to 12.47）and kidneys（from 7.74 to 8.35）were moderate,and increased over time.There was a quick clearance of the activity from the blood circulation.Based on the time-activity curves for 68Ga-NOTA-NFB in the blood samples,majority of the tracer was found in the plasma with negligible accumulation in the red blood cells.The organ with the highest absorbed dose was spleen（193.8±32.5μ Sv/MBq）,followed by liver（119.3±25.0μ Sv/MBq）,kidneys（84.9±9.4μ Sv/MBq）and adrenals（55.2±15.7μ Sv/MBq）.On the other hand,the brain absorbed very low dose（2.7±0.6μSv/MBq）,suggesting that 68Ga-NOTA-NFB does not easily across the blood-brain barrier（BBB）.The mean effective dose was 25.4±6.1μ Sv/MBq.It is much lower than the dose limit of 0.5 Sv per year,as set forth by the Food and Drug Administration（FDA）.68Ga-NOTA-NFB is safety,and can be used repeatedly in year.This tracer is suit for clinical using.2.The characteristics of 68Ga-NOTA-NFB PET imaging in breast cancer.Before the neo-adjuvant chemotherapy,compared the results of PET scan of 68Ga-NOTA-NFB and 18F-FDG.In primary lesions,the SUVmax of 18F-FDG was higher than 68Ga-NOTA-NFB,there was a significant difference between in SUVmax（t=-3.01,P=0.013）,but not in T/NTmax（t=-1.63,P=0.134）,because of the background of 68Ga-NOTA-NFB was lower.On the other hand,in the metastasis in lymph nodes,there was no significant difference in SUVmax（t=-2.02,P=0.072）,but in T/NTmax（t=-2.43,P=0.036）.By comparing the result before and after neo-adjuvant chemotherapy,we found the grade of neo-adjuvant chemotherapy response may have correlation with T/NTmax.Noticeably,we found the statistical correlation between T/NTmax and Ki67（r=0.60,P=0.051）may have difference.Conclusion: 68Ga-NOTA-NFB is safety,and can be used repeatedly in year.This tracer is suit for clinical using.And it can be used in diagnosing breast cancer by PET/CT.And it may have beneficial in evaluating and analyzing the curative effect and prognosis. |
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