奥曲肽及其类似物用于肿瘤治疗的进展

简单综述90Y-奥曲肽、177Lu-奥曲肽在肿瘤治疗中的应用价值。对奥曲肽治疗的原理、在肿瘤及正常组织中的分布、对。肾脏功能的影响和保护剂的应用进行介绍，主要治疗的病种包括不摄取131I的分化型甲状腺癌转移灶、Hurthle细胞甲状腺癌、甲状腺髓样癌、来自胃肠胰的神经内分泌肿瘤、小细胞癌、嗜铬细胞瘤等。对应用适合的剂量和未来新的可能用于临床治疗的放射肽和发展方向加以综述。     

奥曲肽及其类似物用于肿瘤诊断的进展

简要综述111In-奥曲肽和99Tcm-NeoTec在肿瘤诊断中的应用,其对类癌、甲状腺髓样癌、来自胰腺或上消化道的神经内分泌肿瘤的诊断和随访有重要价值,对失去摄碘功能的分化型甲状腺癌、甲亢性突眼、肉样瘤病的肉芽肿过程也可得到阳性结果。应用放射性核素标记的生长抑素类似物使肿瘤成功的显像,可发展并应用标记的类似物来治疗这些肿瘤。生长抑素类似物的标记技术扩展了应用其他肽类进行分子显像的研究兴趣。     

奥曲肽及其类似物用于肿瘤诊断的进展

简要综述^111In-奥曲肽和^99Tc^m-NeoTec在肿瘤诊断中的应用，其对类癌、甲状腺髓样癌、来自胰腺或上消化道的神经内分泌肿瘤的诊断和随访有重要价值，对失去摄碘功能的分化型甲状腺癌、甲亢性突眼、肉样瘤病的肉芽肿过程也可得到阳性结果。应用放射性核素标记的生长抑素类似物使肿瘤成功的显像，可发展并应用标记的类似物来治疗这些肿瘤。生长抑素类似物的标记技术扩展了应用其他肽类进行分子显像的研究兴趣。     

心脏肾上腺素能神经的PET应用

目的研究188Re-奥曲肽在荷瘤裸鼠体内的分布,为进一步肿瘤靶向治疗奠定基础。方法16只荷人H460非小细胞肺癌的BALB／c裸鼠分为4组,经尾静脉注射188Re-奥曲肽 18．5MBq(O．2ml)．于注射后2h,4h,24h,48h每个时间点处死一组裸鼠,取血液、肿瘤组织及主要脏器测量其放射性计数率值,经放射性衰变校正后计算每克组织的百分注射剂量率(％ID／g),观察标记物在动物体内的生物学分布。另2只荷瘤裸鼠同样尾静脉注射相同剂量的188Re-奥曲肽,于注射后相同时间点行SPECT扫描,利用感兴趣区技术对肿瘤／非瘤组织放射性比值(T／NT)进行半定量分析。结果188Re-奥曲肽标记率达(95．3±1．8)％,188Re-奥曲肽在荷瘤裸鼠体内主要分布于肿瘤组织、肝脏、肾脏及肠道,肿瘤部位在4h摄取达到高峰9．8％ID/g,此时SPECT在肿瘤部位有明显的放射性核素浓聚,T／NT在尾静脉药物注射后24h达到高值为7．1。结论 188Re-奥曲肽在BALB／c荷瘤裸鼠体内对人非小细胞肺癌具有靶向定位作用,其在肿瘤部位的分布具有较高的T／NT,188Re．奥曲肽有望用于表达生长抑素受体肿瘤的核素靶向治疗。     

188Re-奥曲肽在荷瘤裸鼠体内分布的实验研究

目的研究188Re-奥曲肽在荷瘤裸鼠体内的分布,为进一步肿瘤靶向治疗奠定基础.方法16只荷人H460非小细胞肺癌的BALB/c裸鼠分为4组,经尾静脉注射188Re-奥曲肽18.5MBq(0.2ml),于注射后2h,4h,24h,48h每个时间点处死一组裸鼠,取血液、肿瘤组织及主要脏器测量其放射性计数率值,经放射性衰变校正后计算每克组织的百分注射剂量率(%ID/g),观察标记物在动物体内的生物学分布.另2只荷瘤裸鼠同样尾静脉注射相同剂量的188Re-奥曲肽,于注射后相同时间点行SPECT扫描,利用感兴趣区技术对肿瘤/非瘤组织放射性比值(T/NT)进行半定量分析.结果188Re-奥曲肽标记率达(95.3±1.8)%,188Re-奥曲肽在荷瘤裸鼠体内主要分布于肿瘤组织、肝脏、肾脏及肠道,肿瘤部位在4h摄取达到高峰9.8%ID/g,此时SPECT在肿瘤部位有明显的放射性核素浓聚,T/NT在尾静脉药物注射后24h达到高值为7.1.结论188Re-奥曲肽在BALB/c荷瘤裸鼠体内对人非小细胞肺癌具有靶向定位作用,其在肿瘤部位的分布具有较高的T/NT,188Re-奥曲肽有望用于表达生长抑素受体肿瘤的核素靶向治疗.     

放射性核素标记奥曲肽诊断小细胞肺癌的研究进展

小细胞肺癌是神经内分泌肿瘤，起源于APUD（胺前体摄取脱羧化）细胞。其细胞表达高水平表达SSTR（生长抑素受体）。奥曲肽是SST（生长抑素）的八肽类似物，它保留了SST类似的活性结构而且有更强的生物学效应和更长的生物半衰期，不易被降解。用放射性核素标记奥曲肽来诊断小细胞肺癌是一种较为理想的无创伤性检查方法。     

放射性核素标记奥曲肽诊断小细胞肺癌的研究进展

小细胞肺癌是神经内分泌肿瘤,起源于APUD(胺前体摄取脱羧化)细胞。其细胞表面高水平表达SSTR(生长抑素受体)。奥曲肽是SST(生长抑素)的八肽类似物,它保留了SST类似的活性结构而且有更强的生物学效应和更长的生物半衰期,不易被降解。用放射性核素标记奥曲肽来诊断小细胞肺癌是一种较为理想的无创伤性检查方法。     

甲状腺癌再分化治疗的研究现状

甲状腺癌虽仅占人类全部恶性肿瘤的1％，但在内分泌系统中是最常见的一类恶性肿瘤。目前甲状腺癌的人群发病率为1／20万～1／30万，2003年美国新增甲状腺癌患者约22000例，其中男性约5700例，女性约16300例。甲状腺癌通常有4种病理类型：乳头状癌（占70％～75％）、滤泡状癌（占15％～20％）、未分化癌（占3％～5％）、髓样癌（占1％～3％）。前2种源于滤泡上皮细胞，总体分化良好，称为分化型甲状腺癌（DTC）。多数DTC恶性程度不高，病程缓慢，即便出现局部转移，也可通过手术、^131Ⅰ内照射、甲状腺激素替代抑制治疗控制病情甚至痊愈。未分化癌恶性程度较高，预后较差。髓样癌源于滤泡旁C细胞，多数病例的临床进展较快，手术是目前主要治疗手段。     

奥曲肽在预防胰腺手术后并发症中的作用

目的　观察奥曲肽在胰腺手术后防止出现并发症中的作用。方法　将 2 1例壶腹周围癌行胰十二指肠切除术的患者随机分为对照组 (n =9)和奥曲肽治疗组 (n =12 ) ,对照组采用常规治疗 ,治疗组除常规治疗外 ,于术后开始应用奥曲肽 0 .1mg 1/8h连续 3～ 5d。 结果　治疗组在术后病情稳定 ,体温波动小 ,胃液、胆汁和胰液的分泌量分别为 (90± 32 )ml/d ,(6 0± 11)ml/d和 (6 5± 2 0 )ml/d ,均较对照组明显减少 (P <0 .0 5 ) ,胰液中淀粉酶为 (5 0 0± 16 2 )U/L ,较对照组明显降低 (P <0 .0 1)。结论　奥曲肽在胰腺手术后 ,减少消化液的分泌 ,尤其在预防胰瘘中发挥重要的作用。     

奥曲肽治疗急性胰腺炎对胃肠动力影响的临床观察

目的观察奥曲肽注射液在治疗急性胰腺炎过程中对患者胃肠动力的影响,从而进一步了解奥曲肽治疗急性胰腺炎的药理作用,充分肯定奥曲肽在治疗急性胰腺炎过程中临床应用。方法在我科近两年收治的急性轻症胰腺炎45例,随机分成治疗组和对照组,治疗组26例,采用醋酸奥曲肽注射液治疗,对照组19例,采用5-氟尿嘧啶治疗。治疗5日后比较两组病人每日胃肠减压引流量,呕吐缓解,肛门排气排便,腹胀症状消失例数。结果两组病人每日胃肠减压引流量无显著差异;而呕吐缓解,肛门排气排便,腹胀症状消失例数,治疗组优于对照组。结论在急性胰腺炎治疗过程中,奥曲肽对胃动力无明显优势作用,但能明显改善患者肠动力。这可能就是奥曲肽治疗急性胰腺炎及其并发症的药理作用之一。     

Targeted systemic radiotherapy of pheochromocytoma and medullary thyroid cancer

Targeted systemic radiotherapy constitutes the systemic administration of a radioactive agent that targets a molecule expressed preferentially on cancer cells. The archetypal such therapy is 131-iodine ((131)I) therapy for differentiated thyroid cancers. Radiotherapy typically delivers a calculated radiation-absorbed dose to tumor that takes into account (contiguous) normal tissue. Systemic radiotherapy development currently uses schema more analogous to chemotherapy--a radioactivity estimate that does not cause any irreversible toxicity. Historically, arbitrary amounts of radioactivity shown to be effective, on the basis of retrospective review, were used for thyroid cancer therapy with (131)I as well as for neuroendocrine tumor therapy with (131)I-labeled meta-iodo-benzylguanidine (MIBG). Their established safety record has led to adaptations that include repeat therapies with nontoxic amounts of radioactivity. There remains, however, a lack of clear understanding of the safety limits of systemic targeted radiotherapy. This is probably most true in systemic therapy with MIBG in adult neuroendocrine tumors. Bone marrow is the primary critical organ for most targeted systemic radiotherapy; second organ involvement may be renal, as with MIBG and targeted radiopeptide therapy, or pulmonary, as with radioimmunotherapy. Most therapies have tended toward multiple administrations of subtoxic amounts of radioactivity. Therapy with MIBG in pheochromococytoma as well as targeted radiopeptide therapy in medullary thyroid cancer has followed this model. Radioimmunotherapy appears very promising; a definitive Phase 2 study needs completion. All therapy has shown promise in extending disease survival (as compared with historical controls), with few major structural (or biochemical) responses. This review will attempt to compliment the excellent existing literature by providing an overall systemic therapeutic approach to this promising endeavor.     

微小RNA在甲状腺癌发生、 发展中的研究进展

微小RNA（miRNA）是一类内源性的、在进化上高度保守的非编码单链小RNA,其在多种生物和代谢过程中发挥着重要作用,包括信号转导及细胞增殖、分化和凋亡。miRNA可以担任抑癌基因或者癌基因,与肿瘤的形成有着密切的联系。近年来的研究结果显示,miRNA与甲状腺癌关系密切,参与了甲状腺癌的发生、发展过程,这与其具有的高侵袭性特征也存在相关性。笔者主要综述miRNA在不同类型甲状腺癌中的最新研究进展。     

钠/碘同向转运体在甲状腺癌131Ⅰ治疗中的应用

钠/碘同向转运体(Na+/I-symporter,NIS)是一种膜蛋白,介导甲状腺滤泡细胞的碘转运,在甲状腺癌的病理生理及131Ⅰ治疗中起着重要的作用.多数研究表明,甲状腺癌的NIS mRNA及蛋白表达水平降低;维甲酸、去甲基化及组蛋白脱乙酰酶抑制剂可刺激失分化甲状腺癌细胞的NIS表达,为甲状腺癌.131Ⅰ的有效治疗进行了有益的探索.NIS基因的克隆和其特性的揭示为甲状腺癌的靶向基因放射治疗提供了可能.     

双能量 CT 碘图及标准化碘浓度对甲状腺癌的诊断价值

目的：探讨双能量CT碘图形态学与碘浓度测定对甲状腺癌的诊断价值。方法回顾性分析行双能量CT增强扫描且经手术病理证实的甲状腺结节患者,分别测量动、静脉期颈内动脉C T值,筛选C T值同时满足动脉期110～250 H U、静脉期70～110 HU共90例（恶性60例,良性30例）。测量正常甲状腺组织,良、恶性结节碘浓度,得出NICnod值（normalized iodine concen‐tration ,标准化碘浓度）,比较良、恶性及正常组间甲状腺结节的差异。对结节形态学分析,分别观察：形态是否规则、沙砾样钙化、结节强化环不完整呈“强化残圈征”、结节突破甲状腺包膜呈“节段缺损征”在诊断恶性结节中的灵敏度、特异性及准确度,比较在碘图及普通图像上的差异。结果①甲状腺癌碘图上,形态不规则、结节强化环不完整呈“强化残圈征”、结节突破甲状腺包膜呈“节段缺损征”诊断为甲状腺癌的灵敏度、特异度及准确度均较普通 CT图像高（P均＜0．05）,沙砾样钙化在碘图与普通图像上无差异（P＞0．05）。②正常与恶性组、正常与良性组及恶性与良性组 NICnod静脉期差异均有统计学意义（Z值分别为－3．092、－3．187、－2．660, P均＜0．05）,动脉期良、恶性组差异无统计学意义。静脉期最佳 NICnod为0．76,小于该值诊断为恶性,受试者工作特征曲线（ROC）的曲线下面积（AUC）值为0．91,敏感度和特异度分别为74．61％、75．60％。③碘图形态学结合结节NICnod诊断甲状腺癌的灵敏度、特异度及准确度分别为：91．67％、86．67％、94．44％。结论双能量C T碘图形态学及碘浓度测量对甲状腺癌的定性诊断有价值。     

分化型甲状腺癌的治疗进展

分化型甲状腺癌作为一种常见的低恶性肿瘤,通过“外科手术+131I治疗+甲状腺激素抑制治疗”三部曲的规范化治疗方案取得了良好的治疗效果。但部分治疗效果差的分化型甲状腺癌逐渐转化为低分化或失分化的难治性甲状腺癌,只能通过增敏和（或）再分化治疗来增加甲状腺癌细胞摄取131I的能力,以期提高131I治疗甲状腺癌的效果。对上述治疗手段无效的难治性甲状腺癌,靶向药物治疗技术的出现为其提供了广阔的治疗前景。笔者对使用增敏剂、再分化诱导剂和靶向药物治疗技术来提高分化型甲状腺癌治疗效果的研究进展进行了综述。     

手术治疗125例分化性甲状腺癌的5年随访结果分析

目的：探讨甲状腺全切除术在治疗分化性甲状腺癌中的临床应用价值。方法：采用我院1988年1月～2001年5月甲状腺全切除术或甲状腺侧叶切除加峡部切除术治疗分化性甲状腺癌125例,对其手术并发症发生、局部复发、转移情况及术后5年生存率进行回顾性对比分析。结果：甲状腺全切除术术后并发症发生率高于甲状腺侧叶切除加峡部切除术组;局部复发、转移率低于侧叶切除加峡部切除术组;5年生存率两组无显著性差异。结论：甲状腺全切除术是治疗甲状腺癌有效的手术方式,但应掌握手术指征,改进、提高手术技术,减少并发症。     

Radiopeptide imaging and therapy in Europe

Receptor targeting with radiolabeled peptides has become an important topic, particularly in nuclear oncology. Strong research efforts are under way in radiopharmaceutical science laboratories and in nuclear medicine departments in Europe. The target receptors belong to the large family of G-protein-coupled receptors. The prototypes of these radiopeptides are based on analogs of somatostatin targeting somatostatin receptor-positive tumors, particularly well-differentiated neuroendocrine tumors. These radiopeptides have an important impact not only on diagnosis but also on targeted radionuclide therapy of these tumors. Besides the registered radiopeptide (111)In-pentetreotide, efficient SPECT tracers labeled with (99m)Tc and PET agents based on generator-produced (68)Ga have been developed and used in the clinic. In parallel to the development of diagnostic agents, radiopeptides labeled with the β(-) emitters (90)Y and (177)Lu are also widely used. Because the same chelators and therefore the same conjugates can be used in diagnosis and therapy, they constitute ideal theranostic pairs. This progress is driven not only by scientists and clinicians but also by patient interest groups. New radiopeptides targeting other G-protein-coupled receptors are entering the clinic, among them glucagon-like peptide 1 receptor-targeting molecules. This receptor is overexpressed on literally all benign insulinomas. (111)In-labeled derivatives of the insulinotropic 39-mer peptide exendin-4 were beneficial in the pre- and perioperative localization of these benign lesions. In contrast, lack of localization may indicate malignant insulinoma. The bombesin- and gastrin-releasing peptide receptor family is potentially important because these receptors are overexpressed on major human tumors such as prostate tumors, breast tumors, gastrointestinal stromal tumors, and vessels of ovarian cancer. (99m)Tc-labeled peptides for SPECT and (68)Ga-, as well as (64)Cu-labeled agonists or antagonists, have been studied in breast tumors, prostate tumors, gastrointestinal stromal tumors, and gliomas with considerable success. A phase I therapeutic study with a (177)Lu-labeled agonist has been completed. There are not enough clinical data available to reveal the significance of these new modalities in patient care, but several phase I studies are under way in larger patient cohorts using PET agents. Another G-protein-coupled receptor with high overexpression on human tumors is the gastrin/cholecystokinin-2 receptor. It is overexpressed in more than 90% of cases of medullary thyroid cancer, in small cell lung cancer, and in a subgroup of neuroendocrine tumors. Correlating with in vitro receptor localization using autoradiography of 27 patients with metastasized medullary thyroid cancer, SPECT or planar imaging of these patients resulted in a 95% sensitivity of tumor localization. Finally, another G-protein-coupled receptor is found in brain tumors and peritumoral vessels. Literally all cases of glioblastoma multiforme overexpress the neurokinin type 1 receptor; the natural ligand is substance P, which was metabolically stabilized, labeled with (90)Y and (213)Bi, and injected into resection cavities or directly into tumors, which were critically located via a catheter system. The major advantage of this approach appeared to be the facilitated resectability of tumors, particularly in those patients who had been treated up front with the locoregional approach. It appears that neoadjuvant treatment before resection is a valid concept. Finally, another peptide family, the arginine-glycine-aspartate-based radiotracers, has made it to the clinic labeled with a variety of radioisotopes for monitoring the integrins α(v)β(3) overexpressed during tumor angiogenesis.     

Metastatic insular thyroid carcinoma: Visualized on Tc-99m pertechnetate,Tc-99m MDP and iodine-131 scintigraphy; a review of the literature for other radionuclide agents

Poorly differentiated insular thyroid carcinoma is classified as a separate entity among other tumors of the thyroid gland. Its histological pattern and clinical course are regarded as intermediate between well-differentiated and anaplastic thyroid cancer. The authors report Tc-99m pertechnetate, Tc-99m MDP and radioiodine imaging features in a 33-year-old male patient with metastatic insular carcinoma of the thyroid. The extent of involvement was almost identical in all three studies. Insular carcinoma of the thyroid was shown by biopsy, and the patient received a cumulative dose of 14,800 MBq (400 mCi) radioactive I-131. Other radionuclide imaging agents are also reviewed.     

1568例甲状腺结节临床及术后病理结果分析

目的分析甲状腺结节的I临床和术后病理的特征,探讨甲状腺结节与分化型甲状腺癌（DTC）的关系。方法将我院收治的1568例甲状腺结节患者电脑资料进行回顾性分析。结果45～54岁是甲状腺结节发生率最高的年龄段;单纯性结节性甲状腺肿是甲状腺结节患者最常见的病理类型,占总数的57．84％;出现甲状腺功能异常的甲状腺结节患者比例达24．87％,其中11．48％为亚临床甲状腺异常;甲状腺结节患者的甲状腺球蛋白抗体（TgAb）阳性率为21．92％,甲状腺过氧化物酶抗体（TPOAb）的阳性率为20．07％。所调查的患者中有907例为单纯性结节性甲状腺肿患者,比例为57．84％,是最常见的病理类型。甲状腺结节患者中DTC发病率为31．63％,且与促甲状腺激素（TSH）呈正向关系,DTC患者的TgAb水平显著高于非DTC患者,但DTC患者和非DTC患者的TPOAb水平差异不明显。结论甲状腺结节患者中DTC患病率最高的年龄阶段是25～34岁和74岁以上,DTC的患病率与患者的TgAh和TSH水平有明显的正相关关系。