~(99m)Tc-RGD-BN在乳腺肿瘤中的诊断价值研究
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摘要
目的:
通过99mTc-RGD-BN在乳腺癌动物模型及健康志愿者的实验研究，评价该新型SPECT显像剂的药代动力学和体内分布特性，证实99mTc-RGD-BN在临床上应用的安全性和可行性。在此基础上针对乳腺癌患者进行99mTc-RGD-BN的SPECT/CT核素显像相关研究，探讨新型SPECT显像分子探针99mTc-RGD-BN的临床应用前景。
方法：
于HYNIC-RGD-BN冻干药盒中加入99mTcO-4，制备出新型的放射性分子探针—99mTc-RGD-BN，通过放射性薄层层析（ITLC）法对新型SPECT显像分子探针99mTc-RGD-BN质量控制进行分析。荷人乳腺癌裸鼠模型制备，并分析99mTc-RGD-BN在荷人乳腺癌裸鼠的体内生物学分布状态，依据SPECT显像结果进一步评价其性质，应用99mTc-RGD-BN对6名正常志愿者（男、女各3名）进行全身SPECT核素显像，依次评估正常志愿者体内的99mTc-RGD-BN药代动力学、在各个时间点的生物学分布、并在此基础上得到其辐射吸收剂量学结果，应用99mTc-RGD-BN SPECT/CT显像对10例乳腺占位患者进行研究，以病理学诊断为金标准同时与超声和钼靶诊断方法的评判结果进行相互对比分析；通过计算SPECT/CT显像中乳腺占位的T/N值结果与测量GRPR、Integrin αvβ3的阳性细胞百分率结果对比分析，探讨乳腺肿瘤的99mTc-RGD-BN放射性摄取与其内Integrinαvβ3、GRPR表达的相关性，最终得到99mTc-RGD-BNSPECT/CT显像对乳腺肿瘤的临床诊断价值的初步结果。
结果：
ITLC法测得99mTc-RGD-BN的标记率在95%以上。乳腺癌T47D荷瘤裸鼠注射99mTc-RGD-BN后体内生物分布结果显示，99mTc-RGD-BN在血液中的放射性摄取较低且清除较快。注射后1h放射性摄取为（0.91±0.21）%ID/g，注射后8h降为（0.07±0.01）%ID/g。注射后1h到8h99mTc-RGD-BN在肾脏的摄取始终很高，保持在（14.54±0.89）%ID/g以上，提示99mTc-RGD-BN主要通过泌尿系统排泄，余脏器、组织均中、低度摄取。肿瘤组织的放射性摄取高，在1h为（4.17±1.12）%ID/g、2h为（3.76±0.67）%ID/g、4h为（2.71±0.64）%ID/g和8h为（1.42±0.35）%ID/g。由SPECT/CT乳腺荷瘤裸鼠99mTc-RGD-BN显像的T/N比值结果，表明注射后4h肿瘤对肌肉、血液、心脏的T/N值达到最高峰，依次为5.17±0.73、17.26±4.06、4.53±1.41。
乳腺癌MDA-MB-435荷瘤裸鼠注射99mTc-RGD-BN后体内生物分布结果显示，99mTc-RGD-BN在血液中的放射性摄取较低且清除较快。注射后1h放射性摄取为（0.88±0.22）%ID/g，注射后8h降为（0.08±0.01）%ID/g。注射后1h到8h99mTc-RGD-BN在肾脏的摄取始终很高，保持在（14.55±0.91）%ID/g以上，提示99mTc-RGD-BN主要通过泌尿系统排泄，余脏器、组织均中、低度摄取。肿瘤组织的放射性摄取高，在1、2、4和8h分别为（4.55±1.08）%ID/g、（3.95±0.69）%ID/g、（2.86±0.65）%ID/g和（1.56±0.32）%ID/g。由SPECT/CT乳腺荷瘤裸鼠99mTc-RGD-BN显像的T/N比值结果，表明注射后4h肿瘤对肌肉、血液、心脏的T/N值达到最高峰，依次为5.53±0.70、18.56±3.98、5.18±1.37。
6名正常志愿者接受99mTc-RGD-BN SPECT全身显像的药代动力学结果表明：99mTc-RGD-BN在人体血液中能够迅速清除，在全身显像10min时，人体内血液的放射性摄入百分比快速下降到（43.05±6.24）%，到注入99mTc-RGD-BN60min时血液的放射性摄入百分比下降到15%左右；注射99mTc-RGD-BN后24h，尿液累计放射性排泄一共占总注入放射性剂量的（73.56±2.04）%。99mTc-RGD-BN注射后不同时间点SPECT全身显像所获得的体内生物学分布数据表明：人体内肝脏有较高的放射性摄取，肾脏呈现非常明显的高放射性摄取，而胃肠道出现了持续偏高的放射性摄取。依据放射性分布数据得到辐射吸收剂量学结果显示：全身辐射吸收剂量为2.17×10-3mSv/MBq，其中辐射吸收剂量最大的是肾脏为2.55×10-2mSv/MBq。
10例患者在行99mTc-RGD-BN SPECT/CT显像时均未出现不适反应，经术后或穿刺病理证实，7例为恶性肿瘤，其中浸润性导管癌5例，原位导管癌与浸润性小叶癌各1例。7例乳腺癌的患者经99mTc-RGD-BN SPECT/CT同机图像融合显像示，占位处放射性摄取均不同程度高于相应正常乳腺组织，T/N比值范围2.56-4.43。另3例经术后或穿刺病理证实为良性乳腺肿瘤，其中2例为乳腺纤维腺瘤，1例为乳腺腺病，99mTc-RGD-BN SPECT/CT同机融合显像图像结果表明乳腺占位处均未见明显的异常放射性增高或浓聚影，T/N比值范围1.01-1.10。同时超声和钼靶对于上述患者诊断也均与病理学结果相符。7例乳腺恶性肿瘤中至少有Integrin αvβ3、GRPR其中之一为表达阳性，单独阳性表达整合素1例、单独阳性表达GRPR2例，两者均为阳性表达的4例。在对1例乳腺占位患者行SPECT/CT显像时，除了可以看到乳腺原发病灶位置有明显的放射性分布异常浓聚外，在其右侧腋下水平也见到了明显的放射性分布异常浓聚，病理回报为淋巴结转移，另1例患者经99mTc-RGD-BN SPECT显像显示除原发灶外还有多根肋骨放射性分布浓聚，后行全身骨扫描及穿刺病理证实为乳腺癌骨转移。通过绘制散点图，发现乳腺占位性病变99mTc-RGD-BN摄取的T/N比值与病变组织的Integrinαvβ3、GRPR表达阳性细胞百分率之间呈线性正相关关系，相关系数r=0.958。
结论：
新型的放射性分子探针99mTc-RGD-BN其标记过程简单快速，同时标记率能够保证。作为一种新型的以Integrin αvβ3和GRPR为双靶点的新型的放射性分子探针，不管在荷人乳腺癌裸鼠模型中还是在健康志愿者的研究中，均具有理想的药代动力学和体内生物分布特性，并具有非常良好的辐射剂量学安全性。应用到乳腺占位患者的临床研究表明，99mTc-RGD-BN对乳腺癌临床诊断具有一定价值，尤其是在对远处转移病灶的检测方面对比传统检查方法具有一定优势。99mTc-RGD-BN显像肿瘤T/N比值与Integrin αvβ3和GRPR的表达之间具有正相关性，印证了99mTc-RGD-BN因其靶向Integrin αvβ3和GRPR，从而作为新型的放射性分子探针的显像定位机制。
Objective:
This study was aimed to explore the feasibility of99mTc-RGD-BN for breasttumor imaging by evaluating correlated pharmacokinetics and biodistribution in nudemouse models bearing human breast carcinoma xenografts, followed by a pilot cinicaltrial involving recruited healthy volunteers, and further confirm the diagnostic valuesthrough the study of99mTc-RGD-BN SPECT/CT imaging in breast tumor patients.
Methods:
The novel radioactive small molecular probe--99mTc-RGD-BN was prepared byHYNIC-RGD-BN lyophilized kits in a solution with Na99mTcO-4agents. Weperformed quality control for this purification process via Radioactive thin-layerchromatography (RTLC). The biodistribution and99mTc-RGD-BN SPECT/CTimaging in nude mouse models bearing human breast carcinoma were assessed forfurther usage in tumor imaging.
In our pilot clinical trial,6healthy volunteers received a mean740-MBq dose of99mTc-RGD-BN administered through bolus injection in the arm. The safety andfeasibility were estimated through evaluations of pharmacokinetics, biodistribution atdifferent time points on the radiation dose of the volunteers. We also recuited10breast tumor patients for99mTc-RGD-BN SPECT/CT imaging. According to thefindings in pathological analysis, the correlation between radioactive uptake andexpression of integrin αvβ3or/and GRPR was assessed by calculating the ratios oftumor and non-tumor (T/N) and the percentage of positive cells in integrin αvβ3or/and GRPR staining. Then, the diagnostic valutes of99mTc-RGD-BN SPECT/CTimaging for breast tumor was evaluated.
Results:
The labeling yields was over95%by RTLC analysis. In the T47D nude mousexenograft model with human breast cancer, the99mTc-RGD-BN biodistributionshowed a low uptake and rapid clearance in blood stream (from (0.91±0.21)%ID/g of 1h to (0.07±0.01)%ID/g of8h). The kidneys maintained a high uptake value of(14.54±0.89)%ID/g at8h post-injection, which revealed a renal clearance of99mTc-RGD-BN. Other organs showed moderate or low uptake ratios. While thetumors had relatively high uptake values, as (4.17±1.12)%ID/g,(3.76±0.67)%ID/g,(2.71±0.64)%ID/g and (1.42±0.35)%ID/g at1,2,4and8h, respectively. The T/Nratios in99mTc-RGD-BN imaging of the T47D nude mouse showed that a highest ratioof tumor to blood, tumor to heart and tomor to muscle at4h after injection(17.26±4.06、4.53±1.41and5.17±0.73, respectively).
In MDA-MB-435nude mouse xenograft model of human breast cancer, afterinjection of99mTc-RGD-BN, the biodistribution showed a low uptake and rapidclearance in blood (from (0.88±0.22)%ID/g of1h to (0.08±0.01)%ID/g of8h). Thekidneys maintained a high uptake value of (14.55±0.91)%ID/g at8h after injectionrevealling the renal clearance of99mTc-RGD-BN. The other organs showed moderateor low uptakes. The tumors had relatively high uptake values of (4.55±1.18)%ID/g,(3.95±0.69)%ID/g,(2.86±0.65)%ID/g and (1.56±0.32)%ID/g at1,2,4and8h,respectively.The T/N ratios in99mTc-RGD-BN imaging of the MDA-MB-435nudemouse showed that the highest ratio of tumor to blood, tumor to heart and tomor tomusle apeared at4h after injection (18.56±3.98、5.18±1.37and5.53±0.70,respectively).
The pharmacokinetics of6healthy volunteers who accepted99mTc-RGD-BNinjection quickly removed the radioactive tracer in the blood. The radioactive uptakerate of the blood (43.05±6.24)%at10minutes, and the blood clearance extended byabout85%in60minutes. The excreted urine radioactivity showed a peak within inthe first24hours, about (73.56±2.04)%of total injection dose excretion in urine.
After injection of99mTc-RGD-BN, at different time points, SPECT body imagingof in vivo biodistribution showed that a higher intake of radioactive in human bodyliver, kidneys and gastrointestinal. The basal body radiation absorbed dose for theradioactive distribution was2.17×10-3mSv/MBq, while the radiation absorbed dosein kidney was2.55×10-2mSv/MBq.
In our study, no significant clinical abnormalities or abnormal biochemicaloutputs were recorded. Accepting99mTc-RGD-BN SPECT/CT imaging, sevenmalignant cases were diagnosed, of the10cases further confirmed by pathological examinations, including5invasive ductal carcinoma cases,1ductal carcinoma in situand1invasive lobular carcinoma. During the study,7malignant lesions showedaccumulation of abnormal radioactivities with T/N ratios ranging from2.56to4.43.The rest3were diagnosed as benign cases with2fibroadenoma and1adenosis. Noaccumulation was found in the3benign cases with T/N ratios ranging from1.01to1.10. The diagnostic outcomes of99mTc-RGD-BN SPECT/CT imaging were coincidedwith the ultrasound and mammography.
Further, immunohistochemical staining results showed that integrin αvβ3and/orGRPR was/were expressed in all malignant cases (1case expressed αvβ3,1caseexpressed GRPR,4cases expressed both αvβ3and GRPR). In two imaging positivecases, an axillary lymph metastastic legion and a bone metastastic lesion showedpositve expressions of the two molecules. The T/N ratio and integrin αvβ3and/orGRPR correlation factor (r=0.958) had shown significantly positive connections withthe percentage of positive cells in tumor regions.
Conclusion:
New radioactive molecular probe99mTc-RGD-BN has been lyophilized for kitpreparation, and the tagging process is simple and fast to ensure that the labeling rates.The novel integrin αvβ3and GRPR as targets of novel radioactive molecular probes,in a nude mouse model of human breast cancer or normal human volunteers, hadshowed ideal pharmacokinetic and biodistributional characteristics, as well as a goodradiation dosimetry safety. Throught this study,99mTc-RGD-BN had been shown acertain diagnostic value in breast cancer cases, especially in the detection of distantmetastases compared to the traditional inspection methods in patients with breastplaceholder. Positive correlation between99mTc-RGD-BN imaging T/N ratios ofintegrin αvβ3and GRPR expression confirms that99mTc-RGD-BN as a new type ofradioactive molecules for in vivo imaging.
通过99mTc-RGD-BN在乳腺癌动物模型及健康志愿者的实验研究，评价该新型SPECT显像剂的药代动力学和体内分布特性，证实99mTc-RGD-BN在临床上应用的安全性和可行性。在此基础上针对乳腺癌患者进行99mTc-RGD-BN的SPECT/CT核素显像相关研究，探讨新型SPECT显像分子探针99mTc-RGD-BN的临床应用前景。
方法：
于HYNIC-RGD-BN冻干药盒中加入99mTcO-4，制备出新型的放射性分子探针—99mTc-RGD-BN，通过放射性薄层层析（ITLC）法对新型SPECT显像分子探针99mTc-RGD-BN质量控制进行分析。荷人乳腺癌裸鼠模型制备，并分析99mTc-RGD-BN在荷人乳腺癌裸鼠的体内生物学分布状态，依据SPECT显像结果进一步评价其性质，应用99mTc-RGD-BN对6名正常志愿者（男、女各3名）进行全身SPECT核素显像，依次评估正常志愿者体内的99mTc-RGD-BN药代动力学、在各个时间点的生物学分布、并在此基础上得到其辐射吸收剂量学结果，应用99mTc-RGD-BN SPECT/CT显像对10例乳腺占位患者进行研究，以病理学诊断为金标准同时与超声和钼靶诊断方法的评判结果进行相互对比分析；通过计算SPECT/CT显像中乳腺占位的T/N值结果与测量GRPR、Integrin αvβ3的阳性细胞百分率结果对比分析，探讨乳腺肿瘤的99mTc-RGD-BN放射性摄取与其内Integrinαvβ3、GRPR表达的相关性，最终得到99mTc-RGD-BNSPECT/CT显像对乳腺肿瘤的临床诊断价值的初步结果。
结果：
ITLC法测得99mTc-RGD-BN的标记率在95%以上。乳腺癌T47D荷瘤裸鼠注射99mTc-RGD-BN后体内生物分布结果显示，99mTc-RGD-BN在血液中的放射性摄取较低且清除较快。注射后1h放射性摄取为（0.91±0.21）%ID/g，注射后8h降为（0.07±0.01）%ID/g。注射后1h到8h99mTc-RGD-BN在肾脏的摄取始终很高，保持在（14.54±0.89）%ID/g以上，提示99mTc-RGD-BN主要通过泌尿系统排泄，余脏器、组织均中、低度摄取。肿瘤组织的放射性摄取高，在1h为（4.17±1.12）%ID/g、2h为（3.76±0.67）%ID/g、4h为（2.71±0.64）%ID/g和8h为（1.42±0.35）%ID/g。由SPECT/CT乳腺荷瘤裸鼠99mTc-RGD-BN显像的T/N比值结果，表明注射后4h肿瘤对肌肉、血液、心脏的T/N值达到最高峰，依次为5.17±0.73、17.26±4.06、4.53±1.41。
乳腺癌MDA-MB-435荷瘤裸鼠注射99mTc-RGD-BN后体内生物分布结果显示，99mTc-RGD-BN在血液中的放射性摄取较低且清除较快。注射后1h放射性摄取为（0.88±0.22）%ID/g，注射后8h降为（0.08±0.01）%ID/g。注射后1h到8h99mTc-RGD-BN在肾脏的摄取始终很高，保持在（14.55±0.91）%ID/g以上，提示99mTc-RGD-BN主要通过泌尿系统排泄，余脏器、组织均中、低度摄取。肿瘤组织的放射性摄取高，在1、2、4和8h分别为（4.55±1.08）%ID/g、（3.95±0.69）%ID/g、（2.86±0.65）%ID/g和（1.56±0.32）%ID/g。由SPECT/CT乳腺荷瘤裸鼠99mTc-RGD-BN显像的T/N比值结果，表明注射后4h肿瘤对肌肉、血液、心脏的T/N值达到最高峰，依次为5.53±0.70、18.56±3.98、5.18±1.37。
6名正常志愿者接受99mTc-RGD-BN SPECT全身显像的药代动力学结果表明：99mTc-RGD-BN在人体血液中能够迅速清除，在全身显像10min时，人体内血液的放射性摄入百分比快速下降到（43.05±6.24）%，到注入99mTc-RGD-BN60min时血液的放射性摄入百分比下降到15%左右；注射99mTc-RGD-BN后24h，尿液累计放射性排泄一共占总注入放射性剂量的（73.56±2.04）%。99mTc-RGD-BN注射后不同时间点SPECT全身显像所获得的体内生物学分布数据表明：人体内肝脏有较高的放射性摄取，肾脏呈现非常明显的高放射性摄取，而胃肠道出现了持续偏高的放射性摄取。依据放射性分布数据得到辐射吸收剂量学结果显示：全身辐射吸收剂量为2.17×10-3mSv/MBq，其中辐射吸收剂量最大的是肾脏为2.55×10-2mSv/MBq。
10例患者在行99mTc-RGD-BN SPECT/CT显像时均未出现不适反应，经术后或穿刺病理证实，7例为恶性肿瘤，其中浸润性导管癌5例，原位导管癌与浸润性小叶癌各1例。7例乳腺癌的患者经99mTc-RGD-BN SPECT/CT同机图像融合显像示，占位处放射性摄取均不同程度高于相应正常乳腺组织，T/N比值范围2.56-4.43。另3例经术后或穿刺病理证实为良性乳腺肿瘤，其中2例为乳腺纤维腺瘤，1例为乳腺腺病，99mTc-RGD-BN SPECT/CT同机融合显像图像结果表明乳腺占位处均未见明显的异常放射性增高或浓聚影，T/N比值范围1.01-1.10。同时超声和钼靶对于上述患者诊断也均与病理学结果相符。7例乳腺恶性肿瘤中至少有Integrin αvβ3、GRPR其中之一为表达阳性，单独阳性表达整合素1例、单独阳性表达GRPR2例，两者均为阳性表达的4例。在对1例乳腺占位患者行SPECT/CT显像时，除了可以看到乳腺原发病灶位置有明显的放射性分布异常浓聚外，在其右侧腋下水平也见到了明显的放射性分布异常浓聚，病理回报为淋巴结转移，另1例患者经99mTc-RGD-BN SPECT显像显示除原发灶外还有多根肋骨放射性分布浓聚，后行全身骨扫描及穿刺病理证实为乳腺癌骨转移。通过绘制散点图，发现乳腺占位性病变99mTc-RGD-BN摄取的T/N比值与病变组织的Integrinαvβ3、GRPR表达阳性细胞百分率之间呈线性正相关关系，相关系数r=0.958。
结论：
新型的放射性分子探针99mTc-RGD-BN其标记过程简单快速，同时标记率能够保证。作为一种新型的以Integrin αvβ3和GRPR为双靶点的新型的放射性分子探针，不管在荷人乳腺癌裸鼠模型中还是在健康志愿者的研究中，均具有理想的药代动力学和体内生物分布特性，并具有非常良好的辐射剂量学安全性。应用到乳腺占位患者的临床研究表明，99mTc-RGD-BN对乳腺癌临床诊断具有一定价值，尤其是在对远处转移病灶的检测方面对比传统检查方法具有一定优势。99mTc-RGD-BN显像肿瘤T/N比值与Integrin αvβ3和GRPR的表达之间具有正相关性，印证了99mTc-RGD-BN因其靶向Integrin αvβ3和GRPR，从而作为新型的放射性分子探针的显像定位机制。
Objective:
This study was aimed to explore the feasibility of99mTc-RGD-BN for breasttumor imaging by evaluating correlated pharmacokinetics and biodistribution in nudemouse models bearing human breast carcinoma xenografts, followed by a pilot cinicaltrial involving recruited healthy volunteers, and further confirm the diagnostic valuesthrough the study of99mTc-RGD-BN SPECT/CT imaging in breast tumor patients.
Methods:
The novel radioactive small molecular probe--99mTc-RGD-BN was prepared byHYNIC-RGD-BN lyophilized kits in a solution with Na99mTcO-4agents. Weperformed quality control for this purification process via Radioactive thin-layerchromatography (RTLC). The biodistribution and99mTc-RGD-BN SPECT/CTimaging in nude mouse models bearing human breast carcinoma were assessed forfurther usage in tumor imaging.
In our pilot clinical trial,6healthy volunteers received a mean740-MBq dose of99mTc-RGD-BN administered through bolus injection in the arm. The safety andfeasibility were estimated through evaluations of pharmacokinetics, biodistribution atdifferent time points on the radiation dose of the volunteers. We also recuited10breast tumor patients for99mTc-RGD-BN SPECT/CT imaging. According to thefindings in pathological analysis, the correlation between radioactive uptake andexpression of integrin αvβ3or/and GRPR was assessed by calculating the ratios oftumor and non-tumor (T/N) and the percentage of positive cells in integrin αvβ3or/and GRPR staining. Then, the diagnostic valutes of99mTc-RGD-BN SPECT/CTimaging for breast tumor was evaluated.
Results:
The labeling yields was over95%by RTLC analysis. In the T47D nude mousexenograft model with human breast cancer, the99mTc-RGD-BN biodistributionshowed a low uptake and rapid clearance in blood stream (from (0.91±0.21)%ID/g of 1h to (0.07±0.01)%ID/g of8h). The kidneys maintained a high uptake value of(14.54±0.89)%ID/g at8h post-injection, which revealed a renal clearance of99mTc-RGD-BN. Other organs showed moderate or low uptake ratios. While thetumors had relatively high uptake values, as (4.17±1.12)%ID/g,(3.76±0.67)%ID/g,(2.71±0.64)%ID/g and (1.42±0.35)%ID/g at1,2,4and8h, respectively. The T/Nratios in99mTc-RGD-BN imaging of the T47D nude mouse showed that a highest ratioof tumor to blood, tumor to heart and tomor to muscle at4h after injection(17.26±4.06、4.53±1.41and5.17±0.73, respectively).
In MDA-MB-435nude mouse xenograft model of human breast cancer, afterinjection of99mTc-RGD-BN, the biodistribution showed a low uptake and rapidclearance in blood (from (0.88±0.22)%ID/g of1h to (0.08±0.01)%ID/g of8h). Thekidneys maintained a high uptake value of (14.55±0.91)%ID/g at8h after injectionrevealling the renal clearance of99mTc-RGD-BN. The other organs showed moderateor low uptakes. The tumors had relatively high uptake values of (4.55±1.18)%ID/g,(3.95±0.69)%ID/g,(2.86±0.65)%ID/g and (1.56±0.32)%ID/g at1,2,4and8h,respectively.The T/N ratios in99mTc-RGD-BN imaging of the MDA-MB-435nudemouse showed that the highest ratio of tumor to blood, tumor to heart and tomor tomusle apeared at4h after injection (18.56±3.98、5.18±1.37and5.53±0.70,respectively).
The pharmacokinetics of6healthy volunteers who accepted99mTc-RGD-BNinjection quickly removed the radioactive tracer in the blood. The radioactive uptakerate of the blood (43.05±6.24)%at10minutes, and the blood clearance extended byabout85%in60minutes. The excreted urine radioactivity showed a peak within inthe first24hours, about (73.56±2.04)%of total injection dose excretion in urine.
After injection of99mTc-RGD-BN, at different time points, SPECT body imagingof in vivo biodistribution showed that a higher intake of radioactive in human bodyliver, kidneys and gastrointestinal. The basal body radiation absorbed dose for theradioactive distribution was2.17×10-3mSv/MBq, while the radiation absorbed dosein kidney was2.55×10-2mSv/MBq.
In our study, no significant clinical abnormalities or abnormal biochemicaloutputs were recorded. Accepting99mTc-RGD-BN SPECT/CT imaging, sevenmalignant cases were diagnosed, of the10cases further confirmed by pathological examinations, including5invasive ductal carcinoma cases,1ductal carcinoma in situand1invasive lobular carcinoma. During the study,7malignant lesions showedaccumulation of abnormal radioactivities with T/N ratios ranging from2.56to4.43.The rest3were diagnosed as benign cases with2fibroadenoma and1adenosis. Noaccumulation was found in the3benign cases with T/N ratios ranging from1.01to1.10. The diagnostic outcomes of99mTc-RGD-BN SPECT/CT imaging were coincidedwith the ultrasound and mammography.
Further, immunohistochemical staining results showed that integrin αvβ3and/orGRPR was/were expressed in all malignant cases (1case expressed αvβ3,1caseexpressed GRPR,4cases expressed both αvβ3and GRPR). In two imaging positivecases, an axillary lymph metastastic legion and a bone metastastic lesion showedpositve expressions of the two molecules. The T/N ratio and integrin αvβ3and/orGRPR correlation factor (r=0.958) had shown significantly positive connections withthe percentage of positive cells in tumor regions.
Conclusion:
New radioactive molecular probe99mTc-RGD-BN has been lyophilized for kitpreparation, and the tagging process is simple and fast to ensure that the labeling rates.The novel integrin αvβ3and GRPR as targets of novel radioactive molecular probes,in a nude mouse model of human breast cancer or normal human volunteers, hadshowed ideal pharmacokinetic and biodistributional characteristics, as well as a goodradiation dosimetry safety. Throught this study,99mTc-RGD-BN had been shown acertain diagnostic value in breast cancer cases, especially in the detection of distantmetastases compared to the traditional inspection methods in patients with breastplaceholder. Positive correlation between99mTc-RGD-BN imaging T/N ratios ofintegrin αvβ3and GRPR expression confirms that99mTc-RGD-BN as a new type ofradioactive molecules for in vivo imaging.
引文
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