In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

Purpose The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).Methods cMAb U36 was labelled with ²¹¹At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with ¹²⁵I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with ¹³¹I-labelled cMAb U36 (directly labelled).Results Comparisons between ²¹¹At-cMAb U36 and ¹²⁵I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for ²¹¹At-cMAb U36, with about 10% cell survival at 50 decays per cell. The ¹³¹I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.Conclusion These results indicate that ²¹¹At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.     

Evaluation of therapeutic response using iodine-131-B72.3 monoclonal antibody in patients with ovarian carcinoma

We used radiolabelled monoclonal antibodies (MoAbs) to prove disease persistence after treatment for ovarian carcinoma. Twelve patients with histologically confirmed ovarian carcinoma were studied. They received 5 mCi (1 mg) of iodine-131-B72.3 by intravenous injection before and after a complete course of chemotherapy. Images were obtained with a LFOV gamma camera 2 h after MoAb administration and daily up to 6 days. Before treatment 8 patients had a true positive scan. Questionable antibody uptake was observed in 2 patients while 1 had a true negative scan and 1 a false-negative examination. After treatment the therapeutic response was evaluated. Five patients had partial remission and antibody scan showed persistence of disease in all patients except 1. Four patients showed progression of the disease and 1 no change. The antibody scan was positive in 4 and questionable in 1. Two patients had complete remission and negative antibody scans. Computed tomography (CT) could not always discriminate postoperative fibrosis from tumour lesions, especially when the peritoneum was involved in the disease. High serum levels of tumour markers were constantly associated with the presence of tumour lesions, but normal values did not guarantee absence of disease. We conclude than the antibody scan is complementary to CT and serum tumor markers in the definition of therapeutic response.Preliminary results were presented at the 2nd International Conference on Diagnosis and Therapy with Monoclonal Antibodies, Naples, Italy, 26–28 April 1990     

Pharmacokinetics and biodistribution of samarium-153-labelled OC125 antibody coupled to CITCDTPA in a xenograft model of ovarian cancer

The use of samarium-153 in the context of radioimmunotherapy of cancers has been limited by the instability of antibody labelling, which produces high uptake concentrations in liver and bone. This study compares the pharmacokinetics and biodistribution of¹⁵³Sm-labelled OC125 monoclonal antibody, in whole or F(ab)₂ fragment form and with diethylene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl diethylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice grafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) expressing CA125 antigen. The specific activity of the immunoconjugates was 18.5–55.5 MBq/mg, and their immunoreactivity exceeded 65%. With¹⁵³Sm-DTPA-OC125F(ab)₂, the stability study in serum indicated that 50% of the metal remained bound to the antibody. The pharmacokinetic study showed a retention half-life of 25.1 h and blood clearance of 0.72 ml/h. The biodistribution study indicated tumour uptake of 4.53%±9% of injected activity per gram (%ID/g) at 24 h and tumour-to-liver and tumour-to-bone ratios of 0.23±0.02 and 1.54±0.49 respectively at 24 h. With¹⁵³Sm-CITCDTPA-OC125F(ab)₂, serum stability was greater (87% of the metal remaining bound to the antibody), retention half-life was 22.25 h and blood clearance was 2.23 ml/h. Tumour was better targeted (8.30%±3.56%ID/g at 24 h), and tumour-to-liver and tumour-to-bone ratios were 1.17±0.36 and 7.08±3.09 respectively at 24 h. However, renal retention remained elevated (29.76%±9.41%ID/g at 24 h). With intact IgG, renal uptake decreased (1.41%±0.49%ID/g at 24 h), but tumour uptake was lower than with fragments (1.46%±0.58%ID/g at 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10±0.05), and blood clearance was slower. The stability and distribution of¹⁵³Sm-CITCDTPA were more favourable than those of¹⁵³Sm-DTPA for application in radioimmunotherapy. Quantitative analysis performed using digitized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for bio-distribution studies of immunoconjugates.     

宫颈癌卵巢移位术后VMAT与IMRT卵巢放疗剂量的比较

目的:比较行卵巢移位术后的宫颈癌患者固定野调强(IMRT)和容积旋转调强(VMAT)计划中卵巢的剂量学差异。方法:31例接受宫颈癌根治术和卵巢移位术,术后需放射治疗的患者,设计9野均分IMRT计划和双弧VMAT计划,在保证靶区处方剂量及危及器官限量的情况下,尽量降低卵巢剂量。分析两种技术卵巢平均剂量的差异,以及卵巢-靶...     

Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma

The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23–76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86 % for PET; 100, 67 and 86 % for CT; and 100, 100 and 100 % for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100 %, specificity of 50 % and accuracy of 90 %. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43 %, and for MRI 86, 100 and 89 %, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI. Received: 9 April 1999; Revised: 22 June 1999; Accepted: 25 August 1999     

Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen.

Monoclonal antibody (Mab) MOv18 preferentially reacts with gynecological carcinomas. We have analyzed the characteristics of murine MOv18 (m-MOv18) and chimeric MOv18 (c-MOv18). We found no differences in affinity and binding to IGROV1 cells between c-MOv18 as IgG and F(ab')2 fragments and m-MOv18. In nude mice bearing IGROV1 xenografts, maximum tumor uptake 6-15 hr after i.v. injection of radiolabeled m-MOv18 IgG, c-MOv18 IgG, c-MOv18 F(ab')2 and a control IgG, 2C7, was 10%, 11%, 3% and 4.5% of the injected dose/g (%ID/g), respectively. M- and c-MOv18 IgG retained this level for several days, while c-MOv18 F(ab')2 and 2C7 cleared rapidly from the tumor. Uptake in normal tissues was low, with the exception of high uptake in kidneys for c-MOv18 F(ab')2. Tumor/blood ratios for c-MOv18 F(ab')2 were sixfold higher than for IgG. Radiation absorbed doses to tumor tissue delivered by 10 microCi iodinated m-MOv18 IgG, c-MOv18 IgG and c-MOv18 F(ab')2 were 39 cGy, 49 cGy and 5 cGy, respectively. A cocktail of 125I-c-MOv18 IgG and 131I-c-MOv18 F(ab')2 injected i.v. into an ovarian cancer patient, localized specifically in the tumor. Ovarian cancer tissue samples obtained 2 days postinjection showed a mean uptake of 1.2 x 10(-3) and 2.7 x 10(-3) %ID/g for c-MOv18 IgG and c-MOv18 F(ab')2, respectively. Results from these in vitro and in vivo experiments indicate that c-MOv18 has promise as a Mab for clinical use.     

The impact of tumour volume and other characteristics on uptake of radiolabelled monoclonal antibodies in tumour tissue of head and neck cancer patients

Radioimmunotherapy (RIT) seems to be a realistic option for eradication of minimal residual squamous cell carcinoma of the head and neck (HNSCC), although uptake levels of radiolabelled monoclonal antibodies (MAbs) in tumour tissue vary strongly. The aim of this study was to obtain greater insight into the factors influencing the accumulation of MAbs in HNSCC. Twenty-seven HNSCC patients were injected with radiolabelled MAb E48 or U36 and underwent surgery 2 days after injection. Radioactivity was measured in tumour biopsies taken from the surgical specimen. Uptake levels were correlated with various patient, tumour and MAb characteristics, including age, sex, site, TNM stage, volume as assesssed by computed tomography or magnetic resonance imaging, degree of differentiation, antigen expression of the tumour, the particular MAb that had been injected and the MAb dose. A stepwise regression multivariate analysis showed that tumour volume is the most significant prognostic factor (P=0.01) for MAb uptake. In conclusion, a significantly higher MAb uptake is found in small tumours as compared to larger tumours. Therefore, RIT may be particularly effective in head and neck cancer patients when used in an adjuvant setting. Received 3 August 1998     

Endobronchial administration of iodine-131 B72.3 monoclonal antibody in patients with lung cancer

We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 Ci (103 g) of Iodine-131-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 Ci (291 g) of ¹³¹I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of ¹³¹I-B72.3 at the tumour site up to 6–9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody ¹³¹I-4C4 was not retained at the tumour site 6 days after MoAb administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers.Preliminary results were presented at the European Nuclear Medicine Congress, August 29-September 2, 1988, Milan, Italy. Offprint request to: S. Del Vecchio     

18F-FDG符合线路显像在卵巢上皮性癌术后监测中的价值

目的探讨18F-脱氧葡萄糖(FDG)符合线路显像在卵巢上皮性癌术后监测中的价值.方法对33例卵巢上皮性癌术后临床完全缓解6个月以上患者进行18F-FDG符合线路显像,经有序子集最大期望值法(OSEM)同时重建衰减与无衰减校正断层图像,用感兴趣区(ROI)技术计算病变/正常组织比值(L/B).并与同期CT、B超结果和血清CA125水平比较.20例施行2次探查术或再次肿瘤细胞减灭术的患者以病理学检查结果进行评判,13例未再次手术者以随访和其他检查结果进行评估.结果18F-FDG符合线路显像24例患者发现异常放射性浓聚灶,3例假阳性.衰减与无衰减校正图像L/B分别为4.9±4.3和4.2±4.0.9例未见异常放射性浓聚灶,4例假阴性.其灵敏度、特异性、准确性、阳性预测值和阴性预测值分别为84.0%、62.5%、78.8%、87.5%和55.6%.与CT、B超结果比较,准确性差异有显著性(x2=4.89、5.0,P均＜0.05).结论18F-FDG符合线路显像能弥补其他影像学检查的不足,增加诊断信息.     

177Lu-FA-DOTA-PEG-PLGA靶向可降解纳米粒子腹腔灌注治疗小鼠卵巢癌伴腹膜转移的实验研究

目的 观察放射性核素¹⁷⁷Lu标记的叶酸-二乙烯三胺五乙酸-聚乙二醇-聚乳酸共聚物(¹⁷⁷Lu-FA-DOTA-PEG-PLGA)纳米粒子的体内靶向分布,评价腹腔灌注纳米粒子治疗小鼠卵巢癌腹膜转移瘤及腹水疗效。方法 制备¹⁷⁷Lu-FA-DOTA-PEG-PLGA纳米粒子,向人卵巢癌移植瘤荷瘤小鼠尾静脉注射纳米粒子后4、24、72 h和7 d,行微型单光子发射计算机断层显像仪(micro-SPECT/CT)显像,观察纳米粒子体内分布情况。将12只人卵巢癌腹腔转移瘤裸鼠模型按随机抽签法分为阴性对照组(生理盐水)、化疗组(顺铂3 mg/kg,2次/周)和粒子组(¹⁷⁷Lu-FA-DOTA-PEG-PLGA粒子18.5 MBq),每组4只,腹腔灌注给药。7 d后行活体荧光成像评价腹腔肿瘤生长情况,计算相对抑瘤率,TUNEL法检测肿瘤细胞凋亡率,免疫组织化学法检测肿瘤Ki67增殖活性,比较治疗后各组腹水体积。结果 micro-SPECT/CT显像显示,移植瘤放射性浓聚,24 h肿瘤肌肉摄取比值(T/M)最高,为2.81±0.49。活体荧光成像显示,腹腔给药治疗后,粒子组、化疗组和阴性对照组的腹腔肿瘤荧光强度分别为(1.45±0.19)×10¹⁰、(2.21±0.36)×10¹⁰和(2.63±0.79)×10¹⁰,差异有统计学意义(F=6.09,P=0.029);粒子组和化疗组的相对肿瘤抑制率(TGI)分别为35.6%和18.6%。粒子组和化疗组的肿瘤细胞凋亡率(AI)均高于阴性对照组(F=9.96,P=0.009),粒子组和化疗组的Ki67指数均低于阴性对照组(F=9.93,P=0.013),粒子组和化疗组腹水体积均小于阴性对照组(F=13.43,P=0.006)。结论 ¹⁷⁷Lu-FA-DOTA-PEG-PLGA纳米粒子可行小鼠卵巢癌靶向显像,腹腔灌注后局部滞留和降解吸收,抑制卵巢癌腹膜转移瘤和腹水生长,为晚期卵巢癌伴腹膜转移患者诊疗提供新思路。     

乳腺癌保乳术后两野与多野动态调强的剂量学研究

目的 比较早期乳腺癌保乳术后切线2野动态调强与非共面多野调强放疗治疗靶区和危及器官的剂量学差异。方法 选取40例接受保乳术后放疗的左侧乳腺癌患者,在同一患者CT影像上,利用相同优化条件分别进行切线2野和非共面3、4、5野4种调强治疗计划设计。比较4种计划的靶区剂量分布、心脏、左肺及右侧乳腺受照剂量和体积,以及机器跳数的差异。结果 非共面4、5野调强计划适形度指数（CI）和均匀性指数（HI）均优于切线2野调强计划（P<0.05）,临床靶区（PTV）最大剂量（D_max）小于2野调强计划（P<0.05）,PTV最小剂量（D_min）大于2野调强计划（P<0.05）。3野与2野计划间无明显差异。4种计划的右乳接受5 Gy照射的百分体积（V₅）、心脏接受30 Gy照射的百分体积（V₃₀）及平均剂量（D_mean）、左肺接受20和5 Gy照射的百分体积（V₂₀、V₅）、平均剂量（D_mean）无明显差异,而机器跳数间差异有统计学意义（F=25.63,P<0.05）,2野调强跳数最少,5野最多。结论 保乳术后非共面4、5野调强计划与切线2野调强计划相比,靶区剂量分布更好,不明显增加正常组织、器官的受照射剂量,但机器跳数明显增加。     

Superimposition of computed tomography and single photon emission tomography immunoscintigraphic images in the pelvis: validation in patients with colorectal or ovarian carcinoma recurrence

A method of superimposing computed tomography (CT) and immunoscintigraphic (IS) single photon emission tomography (SPET) slices is presented and has been applied to 10 patients with suspected cancer recurrence. IS was performed with carcinoembryonic antigen (CEA)-specific indium-111 monoclonal antibodies (MoAbs) in 5 patients with colorectal cancer, and with OC125 ¹¹¹In-MoAbs in 5 patients with ovarian cancer. All patients had an abnormal CT image result in the pelvis, which was interpreted 5 times as recurrence, once as doubtful and four times as scar fibrosis. Recurrence was subsequently proven in all patients. Bone scintigraphy (BS) SPET was recorded at the same time as IS. No special technique was used during BS, IS or CT acquisition. CT images were fed into a computer using a CCD camera. Using the internal anatomical landmarks provided by the pelvic bone structures seen on CT and BS, an operator had to select corresponding fiducial points, which were used by the software to register the images. The final results were CT-BS and CT-IS superimposed images. CT-BS images were used for quality control. In all patients, the inspection of CT-BS and CT-IS showed that the registration process is accurate and assists in the co-interpretation of CT and IS images.This work was presented at the EANM congress, Vienna, September 1991 Offprint requests to: J.-C. Liehn     

A prospective evaluation of OC125 and magnetic resonance imaging in patients with ovarian carcinoma

Eighteen patients with suspected primary or recurrent ovarian carcinoma have been investigated in each case by the assay of serum levels of the antigen CA125, immunoscintigraphy using¹³¹I-OC125 antibody and magnetic resonance imaging using a 0.15 Tesla-system. The final diagnosis was confirmed by laparotomy or laparoscopy. Serum levels of CA125 ranged between 5 and 780 units/ml (normal range < 35). Antibody images and MRI were truly positive in 11 patients, 2 of whom were subsequently found to have bowel tumours. MRI showed greater detail of smaller lesions whilst immunoscintigraphy was more suited to the detection of distant metastases. In 7 patients the antibody images were positive whilst the serum marker levels were normal. This pilot study provides a preliminary comparison of the more recent techniques currently being evaluated for the detection of ovarian carcinoma.     

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer

In 11 patients with rectal cancer, a mixture of F(ab)₂ fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3–10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T _1/2 of 21 h. Initially, about 50% of the plasma activity was due to free ¹³¹I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T _1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm³ distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, ¹²³I- or ¹¹¹In- or ^99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents. We conclude that the theoretical advantages of the local administration of ¹³¹I-labelled antibodies for diagnostic purposes in patients with rectal cancer are not limited by our dosimetric data. Nevertheless, we advocate the use of other radiolabels with more appropriate imaging qualities and probably a lower radiation burden. Offprint requests to: E.J. Derksen     

Phase I therapy study of 186Re-labeled chimeric monoclonal antibody U36 in patients with squamous cell carcinoma of the head and neck.

A phase I therapy study was conducted to determine the safety, maximum tolerated dose (MTD), pharmacokinetics, dosimetry, immunogenicity, and therapeutic potential of 186Re-labeled anti-CD44v6 chimeric monoclonal antibody (cMAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC). The potential of a diagnostic study with 99mTc-cMAb U36 to predict the biodistribution of 186Re-cMAb U36 was evaluated. METHODS: Thirteen patients with recurrent or metastatic HNSCC were given 750 MBq 99mTc-cMAb U36 (2 mg) followed 1 wk later by a single dose of 186Re-cMAb U36 (12 or 52 mg) in radiation dose-escalating steps of 0.4, 1.0, and 1.5 GBq/m2. After each administration, planar and SPECT images were obtained, and the pharmacokinetics and development of human antimurine as well as anti-cMAb responses were determined. Radiation absorbed doses to tumor, red marrow, and organs were calculated. RESULTS: Administration was well tolerated, and excellent targeting of tumor lesions was seen in all patients. Dose-limiting myelotoxicity (thrombocytopenia being most prominent) was the only toxicity observed, resulting in grade 4 myelotoxicity in 2 patients treated with 1.5 GBq/m2. The MTD was established at 1.0 GBq/m2, at which a transient grade 3 thrombocytopenia was seen in 1 patient. One patient showed stable disease for 6 mo after treatment at the MTD. The 2 patients with dose-limiting myelotoxicity showed a marked reduction in tumor size. The reduction was of short duration and, therefore, not considered an objective response. Tumor absorbed doses at MTD ranged from 3.0 to 18.1 Gy. Red marrow doses ranged from 20 to 112 cGy (mean, 51 +/- 16 cGy/GBq) and correlated with platelet nadir (r = 0.8; P < 0.01). Pharmacokinetics varied between patients treated at the same dose level and were accurately predicted by the diagnostic procedure. Five patients experienced a human anti-cMAb response, 1 of which was a human antimouse antibody response. CONCLUSION: This study shows that 186Re-cMAb U36 can be safely administered, with dose-limiting myelotoxicity at 41 mCi/m2. The use of cMAb U36 instead of its murine counterpart did not decrease the induction of human antibody responses. The availability of a 99mTc-labeled diagnostic study that can predict the pharmacokinetics of 186Re-cMAb U36 offers the possibility of using such a study for selection of a safe radioimmunotherapy dose.     

^125I粒子植入复发转移鳞癌术后2个月动态剂量研究

目的探讨^125I粒子植入治疗复发转移鳞癌术后2个月动态剂量评价时靶区体积缩小对剂量学参数及疗效、并发症的影响。方法回顾分析2016年7月至2018年11月行^125I粒子植入治疗复发转移鳞癌患者31例,粒子活度0.5~0.8 mCi,处方剂量100~120 Gy。按术后2个月体积缩小百分比分为小于20%(A组)、20%~40%(B组)、大于40%(C组)。观察D90(90%靶体积接受的剂量)、V90(90%处方剂量覆盖的体积占靶体积的百分比)、V100、V150变化,及疗效、并发症。结果A、B两组各剂量学参数较术后即刻减小,差异具有统计学意义(P<0.05);C组V90、V100、V150较术后即刻差异均无统计学意义(P>0.05),D90较术后即刻减小,差异具有统计学意义(P<0.05);C组各剂量学参数差值百分比均大于A、B组(P<0.05)。A、B、C组局部控制率分别为70%、100%、100%,有效率为0、20%、54.5%;三组均未观察到并发症。结论术后2个月肿瘤缩小速度大于40%,疗效更好,但可能出现局部高剂量区,若邻近重要组织器官,存在并发症风险;当小于20%时,靶区内剂量分布不均匀,可能剂量不足,有复发风险。     

Specific and nonspecific immunoassays to detect HAMA after administration of indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody to patients with ovarian cancer.

The development of human anti-mouse antibodies (HAMA) may cause problems in radioimmunotargeting studies, but may also improve survival of patients. To identify the presence of HAMA in blood samples from patients intravenously injected with 1 mg of 111In-labeled OV-TL3-F(ab')2, we developed three specific OV-TL 3-based HAMA assays and tested these along with two commercially available nonspecific HAMA assays (Sorin and Immunomedics). The specific assays were positive for HAMA with 10 postinjection serum samples from 7 patients. Eight of the 10 samples were also HAMA positive with one or both nonspecific HAMA assays. Conflicting results were observed with half the number of samples. The two nonspecific assays also reacted positively with another 11 serum samples from 5 patients including their preinjection samples. Despite some contradictory results, the nonspecific HAMA assays identify both pre-existent and Mab-induced HAMA, whereas the specific OV-TL3-based HAMA assays identify specific immune-responses occurring after the OV-TL 3 injection.     

SARS恢复期患者特异性IgG抗体滴度观察与分析

目的探讨SARS恢复期患者特异性IgG抗体滴度水平及变化趋势,完善SARS感染后免疫的资料。方法采用口。ISA法检测23例SARS患者发病后6个月、12个月2个时间点血清中特异性IgG抗体滴度。以单克隆抗体标记23例患者的PBMC,用流式细胞仪检测HLA-A2的阳性率。结果6个月时IgG抗体滴度的最高值为1：160阳性(4／23),最低值为1：10阴性(1／23),平均滴度为1：57;12个月时IgG抗体的最高滴度仅为1：80阳性(6／23),最低值为1：10阴性(2／23),平均滴度为1：27。2个时间点抗体滴度之间的差异有统计学意义(P=0．002)。23例患者中HLA-A2阳性14例,阳性率60．9％。结论SARS恢复期患者的抗体滴度在半年以后已呈现明显的下降趋势,目前所依据的SARS-IgG抗体诊断标准是合理可行的。HLA-A2抗原肽疫苗可以治疗和预防50％左右的SARS病毒感染。     

宫颈癌初始治疗后腹主动脉旁淋巴结转移调强放疗的临床观察

目的 对比单纯调强放疗(IMRT)与IMRT同步TP方案化疗治疗宫颈癌初始治疗后腹主动脉旁淋巴结(PALN)转移的疗效和不良反应.方法 选取2008年10月至2013年8月宫颈癌初始治疗后出现PALN转移的56例患者,PALN转移病灶给予放疗剂量GTV 55～60 Gy,CTV45 ～ 50 Gy,共25 ～ 30次,5～6周,接受同步放化疗(CRT组)者36例,单纯放疗(RT组)者20例.CRT组的同步化疗方案为TP方案,第1天紫杉醇135 mg/m2,顺铂60 mg/m2 2 d,21 d重复.单纯PALN转移(iPALN)患者33例,合并其他部位复发转移(niPALN)患者23例.结果 中位随访时间22.7个月(2.7 ～74.4个月).98.2％(55/56)的患者完成了放疗,CRT组中,38.9％的患者完成化疗2～3个周期,61.1％的患者完成化疗1个周期.CRT和RT组的有效率(CR +PR)分别为91.7％(33/36)和85％ (17/20)(x2=0.516,P＞0.05).两组患者的中位总生存(OS)时间为38和23个月,3年OS率分别为57.5％和32.7％ (x2 =4.059,P＜0.05),中位无进展生存时间(PFS)为68.3和16个月,3年PFS率分别为50.4％和29.2％(x2=4.184,P＜0.05).单纯PALN转移(iPALN)(33例)患者与合并其他部位复发转移(niPALN)患者(23例)的中位OS分别为71.2和21.4个月,3年OS率分别为53％和39.5％(x2=4.265,P＜ 0.05).CRT和RT组出现3或4级白细胞低下的患者分别为10例(27.8％)和6例(30％),3级消化道反应各有1例,差异均无统计学意义(x2=0.693、0.847,P＞ 0.05).结论 IMRT同步TP化疗对PALN转移的患者近期效果和远期生存均优于单纯放疗的患者,且不良反应可耐受.     

SARS康复期患者半年血清抗体、肺功能和影像学资料分析

目的了解SARS康复者SARS冠状病毒特异性IgG抗体、肺功能和肺部影像学的变化。方法293例北京地区SARS患者康复后半年内定期进行SARS冠状病毒特异性IgG抗体、肺功能和胸部影像学检查,合并有肺弥散功能异常的康复者定期进行肺功能和胸部影像学复查,动态观察肺功能的恢复情况。部分合并有骨关节疼痛的患者进行股骨头磁共振检查。结果293例中有233例SARS冠状病毒特异性IgG抗体阳性(79．5％),且半年内抗体水平有逐渐下降趋势。特异性IgG抗体阳性的康复者中56例合并有肺部影像学异常,57例(24．5％)合并有弥散功能(D1CO)异常,其中40例半年内进行了3次以上肺功能检查,发现其肺功能和肺部影像学变化均有不同程度的改善。60例进行股骨头磁共振检查的康复者中有15例发现有股骨头缺血性坏死改变(25％)。结论临床诊断为SARS的患者中可能有部分为误诊病例,SARS康复者合并的肺纤维化改变在一定时期内可明显吸收和好转,部分康复者合并有股骨头缺血性坏死改变。