～（99）Tc～m-N-NOET显像对于肿瘤良恶性的鉴别诊断
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摘要
目的：99Tcm-N-NOET [99锝m-氮-二（氮-乙基-氮-乙氧基二硫代氨基甲酸盐）]是一种中性脂溶性心肌显像剂。最近实验室和临床研究资料表明它还可被用作非特异性肿瘤阳性显像剂，其摄取与细胞的代谢和血流有关，能有效地反映肿瘤细胞活性，并且可以区别存活和坏死的肿瘤组织。99Tcm-MIBI是目前应用较多的非特异性肿瘤阳性显像剂，在肺癌、乳腺癌、甲状腺癌等原发和转移灶的诊断中作用较大。本研究对21例甲状腺结节、8例乳腺肿块、24例颅内占位的患者进行了99Tcm-N-NOET显像，以探究该药物在肿瘤性质判断上的临床应用价值，并与MIBI进行了对比。
方法：根据肉眼观察显像剂浓聚程度，并将结果用4分法进行评分，未见显像剂聚集为0分，少量聚集为1分，浓聚为2分，高度浓聚为3分。0-1分为阴性，2-3分为阳性。图像的半定量分析采用计算机ROI技术在结节处取6×6 pixel的感兴趣区（ROI1），并在对侧甲状腺相应区域取相同大小的感兴趣区（ROI2），分别测定每个pixel的平均计数，并计算两者的比值（ROI1/ ROI2）即肿瘤组织计数与正常甲状腺组织比值(T/N)。部分患者进行了MIBI对照检查，所有患者于显像后2周内进行了手术。
结果：恶性病变中有4例甲状腺癌，NOET均有放射性填充，其中颈淋巴结转移的1例，颈部转移灶可见放射性浓聚；4例乳腺癌的患者， NOET均有放射性聚集；7例恶性脑肿瘤，NOET脑显像5例有放射性聚集，2例假阴性病例中有1例为转移性癌。良性病变中，17例良性甲状腺结节有2例NOET有放射性填充；4例良性乳腺肿块有1例NOET有放射性聚集；17例颅内占位良性病变有2例NOET有放射性聚集，其中1例为纤维母细胞型脑膜瘤（细胞增生极度活跃）。
结论：99Tcm-N-NOET可以在恶性肿瘤组织中聚集，而很少在良性病变中聚集，较99Tcm-MIBI假阳性病例数明显少，因此有望成为一种新型的肿瘤阳性显像剂。
Purpose: 99Tcm-N-NOET is a neutral lipophilic myocardial perfusion agent. Recently laboratory and clinical researches find that it can also be used as an tumor positive imaging agent and its concentrated degree is associated with cell metabolism and blood flow, so NOET can reflect the viability of tumor cell effectively and distinguish live tumor tissue with dead. The purpose of this study was to estimate the utility of NOET in the diagnosis of tumor.
Method: We use 4 score system to perform naked-eye analysis according to the concentrated level. 0 score means no accumulation, 1 score small amount of accumulation, 2 score concentration, 3 score obvious concentration. 0-1 score is negative, 2-3 positive. The uptake ratios(the average pixel counts of tumor /the mean pixel counts of normal tissue at the mirror imaging of tumor, UR or T/N) were calculated in patients use the ROI technique. Some of them underwent MIBI imaging also. All patients operated after imaging during 2 weeks.
Results: Among malignant lesions, NOET is concentrated on all thyroid and breast cancer patients and 5 out of 7 brain cancer patients. Among benign lesions, 2 out of 17 benign thyroid nodules, 1 case of benign breast lesion and 2 out of 17 benign intracranial occupying lesions including 1 case of meningoma of fibroblast type (polar hyperplasia) can concentrate NOET.
Conclusion: This preliminary results indicate that NOET can be concentrated on malignant lesions, but it is few concentrated on benign nodules and the false positive cases are less than MIBI. So it may be a more suitable new tumor positive agent.
方法：根据肉眼观察显像剂浓聚程度，并将结果用4分法进行评分，未见显像剂聚集为0分，少量聚集为1分，浓聚为2分，高度浓聚为3分。0-1分为阴性，2-3分为阳性。图像的半定量分析采用计算机ROI技术在结节处取6×6 pixel的感兴趣区（ROI1），并在对侧甲状腺相应区域取相同大小的感兴趣区（ROI2），分别测定每个pixel的平均计数，并计算两者的比值（ROI1/ ROI2）即肿瘤组织计数与正常甲状腺组织比值(T/N)。部分患者进行了MIBI对照检查，所有患者于显像后2周内进行了手术。
结果：恶性病变中有4例甲状腺癌，NOET均有放射性填充，其中颈淋巴结转移的1例，颈部转移灶可见放射性浓聚；4例乳腺癌的患者， NOET均有放射性聚集；7例恶性脑肿瘤，NOET脑显像5例有放射性聚集，2例假阴性病例中有1例为转移性癌。良性病变中，17例良性甲状腺结节有2例NOET有放射性填充；4例良性乳腺肿块有1例NOET有放射性聚集；17例颅内占位良性病变有2例NOET有放射性聚集，其中1例为纤维母细胞型脑膜瘤（细胞增生极度活跃）。
结论：99Tcm-N-NOET可以在恶性肿瘤组织中聚集，而很少在良性病变中聚集，较99Tcm-MIBI假阳性病例数明显少，因此有望成为一种新型的肿瘤阳性显像剂。
Purpose: 99Tcm-N-NOET is a neutral lipophilic myocardial perfusion agent. Recently laboratory and clinical researches find that it can also be used as an tumor positive imaging agent and its concentrated degree is associated with cell metabolism and blood flow, so NOET can reflect the viability of tumor cell effectively and distinguish live tumor tissue with dead. The purpose of this study was to estimate the utility of NOET in the diagnosis of tumor.
Method: We use 4 score system to perform naked-eye analysis according to the concentrated level. 0 score means no accumulation, 1 score small amount of accumulation, 2 score concentration, 3 score obvious concentration. 0-1 score is negative, 2-3 positive. The uptake ratios(the average pixel counts of tumor /the mean pixel counts of normal tissue at the mirror imaging of tumor, UR or T/N) were calculated in patients use the ROI technique. Some of them underwent MIBI imaging also. All patients operated after imaging during 2 weeks.
Results: Among malignant lesions, NOET is concentrated on all thyroid and breast cancer patients and 5 out of 7 brain cancer patients. Among benign lesions, 2 out of 17 benign thyroid nodules, 1 case of benign breast lesion and 2 out of 17 benign intracranial occupying lesions including 1 case of meningoma of fibroblast type (polar hyperplasia) can concentrate NOET.
Conclusion: This preliminary results indicate that NOET can be concentrated on malignant lesions, but it is few concentrated on benign nodules and the false positive cases are less than MIBI. So it may be a more suitable new tumor positive agent.
引文
Decaussin M, Bernard MH, Adeleine P, et al. Thyroid carcinomas with distant metastases: a review of 111 cases with emphasis on the prognostic significance of an insular component. Am J Surg Pathol 2002; 26: 1007–15.
Pierie JP, Muzikansky A, Gaz RD, et al. The effect of surgery and radiation therapy on outcome of anaplastic thyroid carcinoma. Ann Surg Oncol 2002; 9: 57–64.
Livolsi VA, Baloch ZW. Predicting prognosis in thyroid carcinoma: can histology do it? Am J Surg Pathol 2002; 26: 1064–5.
Nguyen G-K, Akin MM. Cytopathology of insular carcinoma of the thyroid. Diagn Cytopathol 2001; 25: 325–30.
Gobien RP. Aspiration biopsy of solitary thyroid nodule. Radiol Clin North Am 1979; 17: 543-554.
Cox MR, Marshall SG, Spence RA: Solitary thyroid nodule: a prospective evaluation of nuclear scanning and ultrasonography. Br J Surg 1991, 78:90–93.
Sathekge MM, Mageza RB, Muthuphei MN, et al.: Evaluation of thyroid nodules with technetium-99m MIBI and technetium-99m pertechnetate. Head Neck 2001, 23:305–310.
Sinha PS, Beeby DI, Ryan P: An evaluation of thallium imaging for detection of carcinoma in clinically palpable solitary, nonfunctioning thyroid nodules. Thyroid 2001, 11:85–89.
Lin CC, Sunday SS, Yang MD, et al.: The use of dual phase 201Tl thyroid scan for equivocal fine needle aspiration results in cold thyroid nodules. Anticancer Res 2001, 21:2969–2972.
Stalteri MA, Parrott SJ, Griffiths VA, et al. Uptake of 99mTc-nitrido dithiocarbomate complexes by tumor cells. Nucl Med Commun, 1997, 18: 870-877.
De Beco V, Moretti JL, Duran Cordobes M, et al. Uptake of 99mTc-N-NOEt
in cancer lines sensitive and resisitant to chemotherapy: comparison with 99mTc-sestamibi (Abstract). J Nucl Med, 1996, 37: 189-190P.
Kosuda S, Katayama M. Technetium-99m tetrofosmin and technetium-99m sestamibi imaging of multiple metastases from differentiated thyroid carcinoma. Eur J Nucl Med, 1995, 22: 1218-1220.
Stalteri MA, Parrott SJ, Griffiths VA, et al. Uptake of 99mTc-nitrido dithiocarbomate complexes by tumor cells. Nucl Med Commun, 1997, 18: 870-877
邢诗安，张永学，安锐. 宫颈癌细胞摄取99mTc-N-(NOEt)2与99mTc-MIBI动力学对比研究，中华核医学杂志，2002，22（6）：363-365
苏敏，刘长江等. 99Tcm-MIBI甲状腺结节显像对甲状腺癌的诊断价值，中华核医学杂志，1998，3（3）：32
阚秀编著. 乳腺癌临床病理学. 北京医科大学. 中国协和医科大学联合出版社，1993. 1
Longman A J , Mishel M H , et al. Side effects burden in women with breast cancer. Cancer Practice, 1996, 4 ( 5 ) : 274-280 .
Ganz P A , Schag H L . Assessing the quality of life : a study in newly-diagnosed breast cancer patients . J Chin Epidemiology , 1990 , 43 (1) :75-86 .
Fallowfield L J , Hall A , Maguire GP ,et al . Psychological outcome of different treatment polices in women with early breast cancer outside a clinical trial . BMJ ,1990 ,301(22) :575-80
Wolberg W H , Tanner MA , Loh WY , et al. Factor influencing options in primary breast cancer treatment . J Chronic Dis ,1987 , 40 :529-34 .
Fisher B , Anderson S , Redmond C , et al . Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing local mastectomy with lumpectomy with and without irradiation in the treatment of breast cancer . N Engl J Med ,1995 ,333 :1456
Vilela Filho O, Carneiro Filho O.Gamma probe-assisted brain tumor microsurgical resection: a new technique[J]. Ard. Neuropsiquiatr,
2002 ,60(4):1042-7.
张俊波，王学斌. 一种改进的99mTc-N-(NOEt)2的标记方法及其生物分布，核技术，1999，22（5）：268-270
Delmon-Mongeon LI, Piwnica-Worms D, et al. Uptake of the cation hexakis (2-methoxyisonutylisonitrile) technetium-99m by human carcinoma cell lines in vitro. Cancer Res, 1995 ; 55 : 2198
Carpentier A, Jeannotte S, Verreault J, et al. Preoperative localization of parathyroid lesions in hyperparathyroidism: Relationship between technetium-99m-MIBI uptake and oxyphil cell content. J Nucl Med 1998; 39: 1441-1444
Staundenherz A, Leitha T. Is there a relationship between Tc99m sestamibi uptake and oxyphil cell content in hyperparathyroidism? (Letter) 1999; 40: 1402-1403.
Vattimo A, Bertelli P, Cintorino M et al. Hürthle cell tumor dwelling in hot thyroid nodules: Preoperative detection with technetium-99m-MIBI dual-phase scintigraphy. J Nucl Med 1998; 39: 822-825.
Adalet I, Ko?ak M, Oguz H, Alag?l F, Cantez S. Determination of medullary thyroid carcinoma metastases by 201Tl, 99Tcm-DMSA, 99Tcm-MIBI and 99Tcm-tetrofosmin. Nucl Med Commun 1999; 20: 353-359
Bernard BF, Krenning EP, Nreeman WA et al. 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and in vivo. Nucl Med Biol 1998; 25: 233-240.
Pauwels EKJ, McCready VR, Stoot JHMB, Van Deurzen DFP. The mechanism of accumulation of tumour-localising radiopharmaceuticals. Eur J Nucl Med 1998; 25: 277-305
Cutreno JA, Yospur LS, Klalkhalki I et al. Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malign breast lesions. J Nucl Med 1998; 39: 449-453.
曹剑鸣，李金彪. 99mTc-N-(NOEt)2肺阳性显像对肺癌诊断的临床价值的探讨，中华核医学杂志，2001，12（6）：440-442
Delmon-Mongeon LI, Piwnica-Worms D, et al. Uptake of the cation hexakis (2-methoxyisonutylisonitrile) technetium-99m by human carcinoma cell lines in vitro. Cancer Res, 1995 ; 55 : 2198
Maffioli L, Steens J, Pauwels E, et al. Application of 99mTc sestamibi in oncology[J]. Tumori, 1996, 82(1):12
Chia Hung Kao, Shih Chuan, Tsai Liu TC, et al. P glycoprotein and multidrug resistence-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings[J]. Cancer Res, 2001, 15 (61) : 1412-1414
Ak Ilknur, Gulbas Zafer, Altinel Faruk, et al. Tc-99m MIBI Uptake and Its Relation to the Proliferative Potential of Brain Tumors[J]. Clinical Nuclear Medicine 2003 28(1): 29-33
Alonso Omar. Is 99mTc-sestamibi scintimammography complementary to conventional mammography for detecting breast cancer in patients with palpable masses[J]? J Nucl Med. 2001 Nov; 42(11):1614-162
Chia Hung Kao, Shih Chuan Tsai Liu TC, et al. P glycoprotein and multidrug resistence-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings. Cancer Res, 2001, 15 (61) : 1412-1414
Muriel A, Noreli F, Jean-Marc R, et al. Enhancement of mdr1 gene expression in normal tissue adjacent to advanced breast cancer. Breast Cancer Res Trea, 2000, 61(1): 13-20
Hendrikse NH, Franssen FJF, van der Graaf WTA, et al. 99m-Te-sestamibi is a substate for P-glycoprotein and the multidrug resistance associated protein. Br J Cancer, 1998, 77: 353-358
Taillefer R. The role of 99mTc-MIBI and other conventional radiopharmaceuticals in breast cancer diagnosis. Seminars in Nuclear Medicine 1999; 29: 16-40
Pierie JP, Muzikansky A, Gaz RD, et al. The effect of surgery and radiation therapy on outcome of anaplastic thyroid carcinoma. Ann Surg Oncol 2002; 9: 57–64.
Livolsi VA, Baloch ZW. Predicting prognosis in thyroid carcinoma: can histology do it? Am J Surg Pathol 2002; 26: 1064–5.
Nguyen G-K, Akin MM. Cytopathology of insular carcinoma of the thyroid. Diagn Cytopathol 2001; 25: 325–30.
Gobien RP. Aspiration biopsy of solitary thyroid nodule. Radiol Clin North Am 1979; 17: 543-554.
Cox MR, Marshall SG, Spence RA: Solitary thyroid nodule: a prospective evaluation of nuclear scanning and ultrasonography. Br J Surg 1991, 78:90–93.
Sathekge MM, Mageza RB, Muthuphei MN, et al.: Evaluation of thyroid nodules with technetium-99m MIBI and technetium-99m pertechnetate. Head Neck 2001, 23:305–310.
Sinha PS, Beeby DI, Ryan P: An evaluation of thallium imaging for detection of carcinoma in clinically palpable solitary, nonfunctioning thyroid nodules. Thyroid 2001, 11:85–89.
Lin CC, Sunday SS, Yang MD, et al.: The use of dual phase 201Tl thyroid scan for equivocal fine needle aspiration results in cold thyroid nodules. Anticancer Res 2001, 21:2969–2972.
Stalteri MA, Parrott SJ, Griffiths VA, et al. Uptake of 99mTc-nitrido dithiocarbomate complexes by tumor cells. Nucl Med Commun, 1997, 18: 870-877.
De Beco V, Moretti JL, Duran Cordobes M, et al. Uptake of 99mTc-N-NOEt
in cancer lines sensitive and resisitant to chemotherapy: comparison with 99mTc-sestamibi (Abstract). J Nucl Med, 1996, 37: 189-190P.
Kosuda S, Katayama M. Technetium-99m tetrofosmin and technetium-99m sestamibi imaging of multiple metastases from differentiated thyroid carcinoma. Eur J Nucl Med, 1995, 22: 1218-1220.
Stalteri MA, Parrott SJ, Griffiths VA, et al. Uptake of 99mTc-nitrido dithiocarbomate complexes by tumor cells. Nucl Med Commun, 1997, 18: 870-877
邢诗安，张永学，安锐. 宫颈癌细胞摄取99mTc-N-(NOEt)2与99mTc-MIBI动力学对比研究，中华核医学杂志，2002，22（6）：363-365
苏敏，刘长江等. 99Tcm-MIBI甲状腺结节显像对甲状腺癌的诊断价值，中华核医学杂志，1998，3（3）：32
阚秀编著. 乳腺癌临床病理学. 北京医科大学. 中国协和医科大学联合出版社，1993. 1
Longman A J , Mishel M H , et al. Side effects burden in women with breast cancer. Cancer Practice, 1996, 4 ( 5 ) : 274-280 .
Ganz P A , Schag H L . Assessing the quality of life : a study in newly-diagnosed breast cancer patients . J Chin Epidemiology , 1990 , 43 (1) :75-86 .
Fallowfield L J , Hall A , Maguire GP ,et al . Psychological outcome of different treatment polices in women with early breast cancer outside a clinical trial . BMJ ,1990 ,301(22) :575-80
Wolberg W H , Tanner MA , Loh WY , et al. Factor influencing options in primary breast cancer treatment . J Chronic Dis ,1987 , 40 :529-34 .
Fisher B , Anderson S , Redmond C , et al . Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing local mastectomy with lumpectomy with and without irradiation in the treatment of breast cancer . N Engl J Med ,1995 ,333 :1456
Vilela Filho O, Carneiro Filho O.Gamma probe-assisted brain tumor microsurgical resection: a new technique[J]. Ard. Neuropsiquiatr,
2002 ,60(4):1042-7.
张俊波，王学斌. 一种改进的99mTc-N-(NOEt)2的标记方法及其生物分布，核技术，1999，22（5）：268-270
Delmon-Mongeon LI, Piwnica-Worms D, et al. Uptake of the cation hexakis (2-methoxyisonutylisonitrile) technetium-99m by human carcinoma cell lines in vitro. Cancer Res, 1995 ; 55 : 2198
Carpentier A, Jeannotte S, Verreault J, et al. Preoperative localization of parathyroid lesions in hyperparathyroidism: Relationship between technetium-99m-MIBI uptake and oxyphil cell content. J Nucl Med 1998; 39: 1441-1444
Staundenherz A, Leitha T. Is there a relationship between Tc99m sestamibi uptake and oxyphil cell content in hyperparathyroidism? (Letter) 1999; 40: 1402-1403.
Vattimo A, Bertelli P, Cintorino M et al. Hürthle cell tumor dwelling in hot thyroid nodules: Preoperative detection with technetium-99m-MIBI dual-phase scintigraphy. J Nucl Med 1998; 39: 822-825.
Adalet I, Ko?ak M, Oguz H, Alag?l F, Cantez S. Determination of medullary thyroid carcinoma metastases by 201Tl, 99Tcm-DMSA, 99Tcm-MIBI and 99Tcm-tetrofosmin. Nucl Med Commun 1999; 20: 353-359
Bernard BF, Krenning EP, Nreeman WA et al. 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and in vivo. Nucl Med Biol 1998; 25: 233-240.
Pauwels EKJ, McCready VR, Stoot JHMB, Van Deurzen DFP. The mechanism of accumulation of tumour-localising radiopharmaceuticals. Eur J Nucl Med 1998; 25: 277-305
Cutreno JA, Yospur LS, Klalkhalki I et al. Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malign breast lesions. J Nucl Med 1998; 39: 449-453.
曹剑鸣，李金彪. 99mTc-N-(NOEt)2肺阳性显像对肺癌诊断的临床价值的探讨，中华核医学杂志，2001，12（6）：440-442
Delmon-Mongeon LI, Piwnica-Worms D, et al. Uptake of the cation hexakis (2-methoxyisonutylisonitrile) technetium-99m by human carcinoma cell lines in vitro. Cancer Res, 1995 ; 55 : 2198
Maffioli L, Steens J, Pauwels E, et al. Application of 99mTc sestamibi in oncology[J]. Tumori, 1996, 82(1):12
Chia Hung Kao, Shih Chuan, Tsai Liu TC, et al. P glycoprotein and multidrug resistence-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings[J]. Cancer Res, 2001, 15 (61) : 1412-1414
Ak Ilknur, Gulbas Zafer, Altinel Faruk, et al. Tc-99m MIBI Uptake and Its Relation to the Proliferative Potential of Brain Tumors[J]. Clinical Nuclear Medicine 2003 28(1): 29-33
Alonso Omar. Is 99mTc-sestamibi scintimammography complementary to conventional mammography for detecting breast cancer in patients with palpable masses[J]? J Nucl Med. 2001 Nov; 42(11):1614-162
Chia Hung Kao, Shih Chuan Tsai Liu TC, et al. P glycoprotein and multidrug resistence-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings. Cancer Res, 2001, 15 (61) : 1412-1414
Muriel A, Noreli F, Jean-Marc R, et al. Enhancement of mdr1 gene expression in normal tissue adjacent to advanced breast cancer. Breast Cancer Res Trea, 2000, 61(1): 13-20
Hendrikse NH, Franssen FJF, van der Graaf WTA, et al. 99m-Te-sestamibi is a substate for P-glycoprotein and the multidrug resistance associated protein. Br J Cancer, 1998, 77: 353-358
Taillefer R. The role of 99mTc-MIBI and other conventional radiopharmaceuticals in breast cancer diagnosis. Seminars in Nuclear Medicine 1999; 29: 16-40