~（99m）Tc-MIBI SPECT/CT同机融合显像联合血清CEA对肺占位病变的诊断价值

目的：探讨99mTc-MIBI SPECT/CT同机融合显像联合血清CEA检测对肺占位病变诊断的临床价值。方法：对56例疑是肺占位病变的患者行99mTc-MIBI SPECT/CT同机融合显像与血清CEA检查,分别计算出以上两种方法以及联合应用在诊断肺占位病变的灵敏度、特异性、准确性。结果：两种方法联合使用与单用99mTc-MIBI SPECT/CT同机融合显像相比,灵敏度比较差异有统计学意义（P〈0.05）,而特异度比较差异无统计学意义。两种方法联合使用与血清CEA相比,灵敏度比较差异有统计学意义（P〈0.05）,而特异度比较差异无统计学意义。结论：99mTc-MIBI SPECT/CT同机融合显像联合血清CEA在肺占位病变诊断中具有重要诊断价值。     

新型肿瘤新生血管靶向分子探针99mTc-RRL的合成及初步研究

[目的]探讨新型肿瘤新生血管显像剂99mTc-RRL的合成与标记及其在不同肿瘤动物模型中的初步显像效果,评价99mTc-RRL用于肝癌裸鼠模型体内的生物分布特点。[方法]固相合成法合成RRL,与99mTc进行标记。制备不同类型肿瘤动物模型,并进行单光子计算机断层（SPECT）显像。荷瘤HepG2肝癌裸鼠尾静脉注射99mTc-RRL后,于不同时刻处死动物,取感兴趣器官和组织称重并测量其放射性计数,计算各器官或组织的%ID/g值。同时,高锝酸钠阴性对照组、非标记RRL竞争阻断组采用同样方法,计算其6h时刻各脏器或组织的%ID/g值。HE染色和CD34免疫组化方法用于评价瘤体新生血管状态及分子探针检测阈值的相关性分析。[结果]99mTc-RRL标记率达80%,放射化学纯度高,体外稳定性好。SPECT显像示肿瘤部位见显影,轮廓清晰,放射性明显高于其他器官,随时间延长,肿瘤部位有持续放射性聚集。生物分布数据显示99mTc-RRL血液清除快,肿瘤部位显示放射性持续滞留,提供良好靶/非靶组织比值。HE染色和免疫组化结果显示了瘤体旺盛的血管生成;瘤体大小与探针摄取量呈明显正相关关系。[结论]99mTc-RRL能够特异性地聚集于不同类型肿瘤组织。体内生物分布好,可提供良好的靶/非靶组织比值,是具有应用价值的肿瘤新生血管靶向示踪剂。     

Diffuse Myocardial Uptake of 99mTc-HDP in Multiple Myeloma

Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate (^99mTc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, ^99mTc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM.     

Detection and Characterization of Parathyroid Adenoma/Hyperplasia for Preoperative Localization: Comparison Between 11C-Methionine PET/CT and 99mTc-Sestamibi Scintigraphy

Purpose

¹¹C-Methionine PET/CT (Met-PET/CT) is a useful imaging method for detection of parathyroid adenoma; however, the reported detection rate has been variable. The current study was intended to investigate detection sensitivity and preoperative localization of parathyroid adenoma (PA) or parathyroid hyperplasia (PH) on Met-PET/CT compared with ^99mTc-sestamibi (MIBI) scintigraphy in patients with primary hyperparathyroidism (HPT) or suspected PA.

Methods

Met-PET/CT and MIBI scintigraphy images were reviewed by two nuclear medicine physicians unaware of pathologic results. Detection sensitivities and preoperative localization of detected parathyroid tissues into five predefined segments were evaluated by visual assessment and semi-quantitative analysis with ratio of standardized uptake values (SUVR) between parathyroid tissue and normal lung as reference. Linear regression analysis with SUVR and serum parathyroid hormone (sPTH) was performed for characterization of PA or PH. Predicted PTH (pPTH) was calculated and compared with sPTH in PH and PA. Each pPTH was obtained for a calculated SUVR by using linear regression model from the result of previous linear regression analysis between SUVR and sPTH.

Results

In 16 patients, detection sensitivities of Met-PET/CT and MIBI scintigraphy were 91.7 % (11/12) and 41.7 % (5/12) for PA and PH including both biopsy-confirmed and clinically-suspected cases, and 100 % (8/8) and 50 % (4/8) for pathologically confirmed PA and PH cases only, respectively. Met-PET/CT showed higher performance than MIBI scintigraphy in localization of parathyroid tissues; correct localization rate was 87.5 % (7/8) on Met-PET/CT and 50 % (4/8) on MIBI scintigraphy. In semi-quantitative analysis, SUVR was linearly associated with sPTH by linear regression analysis (sPTH = 39.53 × SUVR − 89.84, p = 0.0383). There was a borderline significant difference in pPTH between PH and PA (35.1 vs 204.7 ± 164.0, p = 0.052), while there was no significant difference in sPTH between PH and PA (289 vs 230.4 ± 160.4, p = 0.305).

Conclusions

Met-PET/CT has a potential to be a useful diagnostic modality for preoperative detection and localization of parathyroid tissues with higher sensitivity than MIBI scintigraphy, and for characterization of PA or PH.     

Diagnostic Performance of Breast-Specific Gamma Imaging (BSGI) for Breast Cancer: Usefulness of Dual-Phase Imaging with 99mTc-sestamibi

Purpose

The aim of this study was to investigate the usefulness of breast-specific gamma imaging (BSGI) with dual-phase imaging for increasing diagnostic performance and interpreter confidence.

Methods

We studied 76 consecutive patients (mean age: 49.3 years, range: 33–61 years) who received 925 MBq (25 mCi) ^99mTc-sestamibi intravenously. Craniocaudal and mediolateral oblique planar images were acquired for all patients. Delayed images were obtained from all patients 1 h after tracer injection, except for patients with no definite abnormal uptake. All images were classified into four categories: group 1 (definite negative) = no definite abnormal uptake; group 2 (possible negative) = symmetrically diffuse and amorphous uptake; group 3 (possible positive) = asymmetrically mild and nodular uptake; group 4 (definite positive) = asymmetrically intense and nodular uptake. To evaluate diagnostic performance, the BSGI studies were classified as positive (group 3 or 4) or negative (group 1 or 2) for malignancy according to a visual analysis. The final diagnoses were derived from histopathological confirmation and/or imaging follow-up after at least 6 months (range: 6–14 months) by both ultrasonography and mammography.

Results

The patients’ ages ranged from 33 to 61 years, with an average of 49.3 years. Thirteen patients were diagnosed with malignancy, and 63 patients were diagnosed as negative for malignancy. Using early images, 43 patients were classified as group 1, 12 as group 2, 10 as group 3 and 11 as group 4. Based on early images, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BSGI were 77 %, 83 %, 48 %, 95 % and 82 %, respectively. Dual-phase BSGI had a sensitivity, specificity, PPV, NPV and accuracy of 69 %, 95 %, 75 %, 94 % and 91 %, respectively. The BSGI specificity was significantly higher with dual-phase imaging than with single-phase imaging (p = 0.0078), but the sensitivity did not differ significantly (p = 1.0). Based on dual-phase imaging, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of BSGI for the evaluation of US BI-RADS 4 lesions were 60 %, 86 %, 67 %, 83 % and 78 %, respectively.

Conclusion

Dual-phase imaging in BSGI showed good diagnostic performance and would be useful for increasing interpreter diagnostic confidence, with higher specificity, positive predictive value and accuracy for breast cancer screening as well as the differential diagnosis of breast disease compared with single-phase imaging.     

A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling

MicroRNAs (miRNAs) dysregulation is critically involved in lung cancer. Regulating miRNAs by natural agents may be a new strategy for cancer treatment. We previously found that a novel small-molecule compound diaporine A (D261), a natural product of endophytic fungus 3lp-10, had potential anti-cancer activites. In the present study, the inhibitory effect of D261 on non-small cell lung cancer (NSCLC) growth and its possible mechanisms involving miRNA regulation were investigated. By cell viability assay, cell proliferation analysis, and clonal growth assay, we proved that D261 effectively inhibited the proliferation of NSCLC cells (NCI-H460 and A549) in vitro. Administration of D261 (5 mg/kg) to NCI-H460 xenografts bearing mice also inhibited tumor growth and decreased the expression of cell proliferation regulator, midkine. Moreover, D261 induced cell cycle arrest with a reduced expression of various G₁/S transition-related molecules including cyclin D1, cyclin E1, CDK4, and CDK2, but without influencing apoptosis in NSCLC cells. Intriguingly, D261 modified expressions of some miRNAs and especially upregulated miR-99a, whose direct target was mammalian target of rapamycin (mTOR). Furthermore, overexpression of miR-99a antagonized the anti-tumor actions of D261 including the suppression of mTOR pathway activation, cell cycle-related proteins and cell growth. In addition, blocking of miR-99a expression by transfection of miR-99a inhibitors before D261 treatment counteracted the anti-tumor effects of D261. These data suggest that miR-99a/mTOR pathway was involved in D261-induced tumor suppression in NSCLC cells. D261 might be a potent anti-cancer agent by upregulating miR-99a expression.     

Oxotechnetium 99mTcO[SN(R)S][S] complexes as potential 5-HT1A receptor imaging agents

A series of ^99mTcO[SN(R)S][S] complexes carrying the 1-(2-methoxyphenyl)piperazine moiety on the tridentate ligand [SN(R)S] was synthesized. For structural characterization and for in vitro binding assays the analogous oxorhenium complexes were prepared. As demonstrated by appropriate competition binding tests in rat hippocampal preparations, all oxorhenium analogues showed affinity for the 5-HT_1A receptor binding sites with IC₅₀ values at the nanomolar range (IC₅₀= 5.8–103 nM). All ^99mTcO[SN(R)S]/[S] complexes showed significant brain uptake in rats at 2 min p.i. (0.24–1.31% ID). However, a clear correlation between distribution of radioactivity in the brain and distribution of 5-HT_1A receptors could not be established.     

Heterogeneity of myocardial wall motion and thickening in the left ventricle evaluated with quantitative gated SPECT

BACKGROUND: Global and regional ventricular function may be evaluated by using gated myocardial perfusion single photon emission computed tomography (SPECT). This study investigated two parameters of regional contraction of the left ventricle, segmental wall motion (WM) and wall thickening (WT), to determine their similarity and disparity in each myocardial segment in patients with normal myocardial perfusion. METHODS AND RESULTS: Thirty-five patients with normal myocardial perfusion and cardiac function (mean left ventricular ejection fraction, 62.6%+/-8.8%) were included in this study. A 1-day stress/rest protocol was used as a means of acquiring technetium 99m (Tc-99m) sestamibi gated SPECT protocol for each patient. A commercially available software package for quantitative gated SPECT (QGS) was used to generate cine loop three-dimensional surface display and SPECT images. The left ventricle was divided into 9 segments to score WM and WT (on a scale of 0 to 4, with 0 being normal and 4 being severely reduced) by 6 independent observers. The WM score was significantly higher than the WT score in the septum, whereas the WM score was lower than the WT score in the inferior segment. Similar WM and WT scores were observed in the remaining segments. CONCLUSIONS: Heterogeneous myocardial WM and WT were observed by using QGS software. These findings suggest that different criteria are required in each segment to evaluate segmental WM and WT by means of gated myocardial perfusion SPECT.     

Sustained reduction of exercise perfusion defect extent and severity with isosorbide mononitrate (Im dur) as demonstrated by means of technetium 99m sestamibi

BACKGROUND: The impact of long-acting nitrates on the extent and severity of stress-induced myocardial ischemia is not well described, especially after long-term treatment. METHODS: Forty patients with chronic stable angina and reversible ischemia on an exercise stress myocardial perfusion single photon emission computed tomography (ex-SPECT) were prospectively studied in a 6-week period. At baseline, rest thallium-201/exercise stress technetium 99m sestamibi SPECT was performed, followed by treatment with extended-release isosorbide 5-mononitrate (5-ISMN, Imdur). Follow-up ex-SPECT was performed 5 days and 6 weeks after the initiation of therapy with extended-release 5-ISMN. The exercise treadmill testing (ETT) protocol and exercise duration of the follow-up studies were the same as that of the baseline ETT. Defect extent and severity were analyzed both by means of an automated quantitative method, with CEqual software, and visually, with a 20-segment scoring system (which was also used to derive a summed stress score [SSS]). RESULTS: In the 6-week study period, significant reductions occurred in both the extent and the severity of exercise-induced ischemia by means of quantitative SPECT (13.8% [P<.0003] and 12.7% [P<.0003], respectively). There was no significant change in these variables between stages 2 (day 5) and 3 (6 weeks), indicating no development of tolerance to the nitrate effect. Similar reductions were noted by means of the visual analysis (SSS reduction of 13.0% [P<.002]) in the entire study period. CONCLUSIONS: Patients with chronic-stable-angina treated with a long-acting nitrate demonstrate improvement in myocardial perfusion defect extent and severity in an extended period by means of both visual and quantitative analysis of sequential exercise testing to the same rate-pressure product end point.