Burggasser Georg, Hurtl Ingrid, Hauff Wolfgang, Lukas Julius, Greifeneder Michaela, Heydari Bamdad, Thaler Arnulf, Wedrich Andreas, Virgolini Irene
Department of Ophthalmology and Optometry, University of Vienna, Vienna, Austria.
J Nucl Med. 2003 Oct;44(10):1547-55.
Receptors for somatostatin (SST) (SSTR) are expressed on various tumor cells as well as on activated lymphocytes. Previous data have shown that (99m)Tc-P829 binds with high affinity to many different types of tumor cells as well as to leukocytes via the human hSSTR2, hSSTR3, and hSSTR5 target receptors. Consequently, (99m)Tc-P829 was successfully introduced as a peptide tracer for tumor imaging. In this study, we evaluated the orbital uptake of (99m)Tc-P829 in patients with active and inactive thyroid-associated orbitopathy (TAO), accompanied by lymphocyte infiltration in the acute stage and by muscle fibrosis in the chronic stage of the disease.
To evaluate its clinical usefulness in Graves' disease, (99m)Tc-P829 scintigraphy (approximately equal to 740 MBq) was performed in 44 patients with TAO (median duration, 19 mo; range, 1-360 mo). The clinical activity of the orbital disease was graded by the NOSPECS (no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) classification of the American Thyroid Association, the clinical activity score (CAS), and the superonasal index (SNI). SPECT (360 degrees ) and planar studies were completed within 3 h after injection. Orbital (O) regions of interest (ROIs) were compared with temporoparietal and occipital (OCC) ROIs. Orbital uptake ratios in Graves' disease were compared with data obtained from lung cancer patients with no eye disease (n = 22).
Overall, (99m)Tc-P829 biokinetics were the same in Graves' disease patients as in lung cancer patients, showing a rapid blood clearance and visualization of the facial bones within minutes of injection. In all control patients, the orbit appeared as a "cold area," whereas visual orbital accumulation of (99m)Tc-P829 was found in patients with active TAO (O/OCC ratios: 1.26 +/- 0.04 vs. 1.69 +/- 0.04; P < 0.01, respectively). Patients with active eye disease (n = 25) presented with an increased orbital uptake of (99m)Tc-P829 compared with patients with inactive disease (n = 19; O/OCC ratio: 1.12 +/- 0.05; P < 0.01). A statistically significant correlation was found between CAS and the orbital uptake (O/OCC ratio) values (r = 0.90), whereas no correlation could be documented regarding the NOSPECS classification as well as the SNI.
In TAO, (99m)Tc-P829 yields high orbital binding with good clinical correlation. The better image quality due to the high energy of technetium, the lower radiation dose for patients and personnel, and the short acquisition protocol favor SSTR scintigraphy with (99m)Tc-P829 over (111)In-labeled compounds. The in-house availability of the radiotracer and cost-effectiveness are further advantages.
生长抑素(SST)受体(SSTR)在各种肿瘤细胞以及活化淋巴细胞上均有表达。既往数据表明,(99m)Tc - P829通过人hSSTR2、hSSTR3和hSSTR5靶受体与多种不同类型的肿瘤细胞以及白细胞高亲和力结合。因此,(99m)Tc - P829已成功作为肿瘤显像的肽类示踪剂引入。在本研究中,我们评估了(99m)Tc - P829在活动期和非活动期甲状腺相关眼病(TAO)患者眼眶中的摄取情况,该病在急性期伴有淋巴细胞浸润,在慢性期伴有肌肉纤维化。
为评估其在格雷夫斯病中的临床应用价值,对44例TAO患者(中位病程19个月;范围1 - 360个月)进行了(99m)Tc - P829闪烁显像(约740 MBq)。眼眶疾病的临床活动度通过美国甲状腺协会的NOSPECS(无体征或症状;仅有体征,无症状;仅有体征;眼球突出;眼肌受累;角膜受累;视力下降)分类、临床活动评分(CAS)和鼻上指数(SNI)进行分级。注射后3小时内完成SPECT(360度)和平面显像研究。将眼眶(O)感兴趣区(ROI)与颞顶叶和枕叶(OCC)ROI进行比较。将格雷夫斯病患者的眼眶摄取率与无眼部疾病的肺癌患者(n = 22)的数据进行比较。
总体而言,(99m)Tc - P829在格雷夫斯病患者中的生物动力学与肺癌患者相同,表现为血液清除迅速,注射后数分钟内即可显示面骨。在所有对照患者中,眼眶表现为“冷区”,而在活动期TAO患者中发现(99m)Tc - P829在眼眶有明显积聚(O/OCC比值:分别为1.26±0.04对1.69±0.04;P < 0.01)。与非活动期疾病患者(n = 19)相比,活动期眼病患者(n = 25)的(99m)Tc - P829眼眶摄取增加(O/OCC比值:1.12±0.05;P < 0.01)。发现CAS与眼眶摄取(O/OCC比值)值之间存在统计学显著相关性(r = 0.90),而关于NOSPECS分类以及SNI则未发现相关性。
在TAO中,(99m)Tc - P829在眼眶有高结合率且与临床有良好相关性。由于锝的能量高、患者和工作人员所受辐射剂量低以及采集方案短,(99m)Tc - P829的SSTR闪烁显像比(111)In标记化合物具有更好的图像质量。该放射性示踪剂的内部可获得性和成本效益是进一步的优势。