经皮瘤内注射32P玻璃微球对肝癌组织的影响

目的探讨经皮瘤内注射~(32)P玻璃微球(~(32)P-GMS)对肝癌瘤组织的影响及其最佳剂量。方法建立24只兔VX2肝癌模型,分为A、B、C、D 4组并分别经皮瘤内注射37、74、111和148个放射性强度单位(MBq)的~(32)P-GMS,7、14和21 d后分批处死实验兔并取注药部位肿瘤组织,在光镜和电镜下观察其病理变化。结果注射~(32)P-GMS剂量与肿瘤细胞的放射性损害相关。A、B组不能完全杀死癌组织;C组肿瘤细胞几乎完全消失,纤维结缔组织对瘤灶形成完整的包绕;D组未见存活的肿瘤组织,但见正常肝组织亦被累及。结论经皮瘤内注射适量的~(32)P-GMS可以最大限度地杀伤瘤组织,本实验显示111 MBg为最佳剂量,对于阻止肝癌转移具有重要意义。     

瘤内注射153Sm-树脂微球治疗肝癌的实验研究

目的：观察瘤内注射^153Sm-树脂微球（RTMS）在荷人肝癌小鼠模型体内的药代动力学和治疗作用。方法：建立荷人肝癌小鼠模型，60只为体内分布研究组，每只小鼠瘤内注射^153Sm-RTMS 18．5MBq，连续计算10d内小鼠血液、肿瘤和各脏器组织的每克组织百分注射剂量（％ID／g)。30只为治疗实验组，再分瘤内注射370 MBq ^153Sm-RTMS和0．1mL生理盐水3个亚组，计算20d内肿瘤缩小率，计数外周血细胞，并作肿瘤病理检查。结果：（1）^153Sm-RTMS瘤内注射后30min的滞留率为94．34％，第8天时仍高达62．21％。（2）少量^153Sm可弥散入血，其全身分布以肺脏为最高，肝脏次之。（3）370和555MBq治疗量均有明显疗效，尤以555MBq组更好。（4）治疗量^153Sm-RTMS对小鼠造血功能无明显影响。结论：^153Sm-RTMS标记牢固、稳定性好，瘤内注射后可长时间滞留在肿瘤组织内，全身扩散量很小，大剂量注射的疗效明显。     

32P胶体小鼠种植肝癌内注射后骨骼放射性的研究

目的:研究肿瘤内单纯注射32P胶体和先注射聚合白蛋白(MAA),再注射32P胶体两种给药方法的骨骼内的放射性动态分布,探讨不同剂量MAA对32P扩散的阻滞效果。方法:在Balb/c小鼠右侧胸前皮下接种H22肝癌细胞,10天后接种部位长出直径约1cm的肿瘤。随机将动物模型小鼠分为4组:A组只注射32P胶体1.85MBq;B组先注射1×104颗粒MAA,再注射32P胶体1.85MBq;C组先注射1×105颗粒MAA,再注射32P胶体1.85MBq;D组先注射1×105颗粒MAA,再注射32P胶体18.5MBq。注射后30min、24h、48h、第8天和第16天时处死小鼠,测定骨骼的放射性。结果:瘤内局部注射32P胶体时,骨骼内可检测到32P的放射性,当向肿瘤内注射的32P胶体前,预先注入MAA组小鼠,其骨骼32P分布均比未注射MAA的一组明显少,其中1×105颗粒MAA组的小鼠,32P骨骼的分布又比1×104颗粒MAA组少;当预先注入的MAA颗粒数量相同时,注射的32P胶体剂量加,骨骼分布亦随之增加。结论:与单纯瘤内注射32P胶体相比,先在瘤内注入MAA,再注入32P胶体,MAA可以有效阻止32P胶体的扩散,减少了32P骨骼分布,从而减少骨髓抑制副作用的发生率。     

32制剂内照射治疗难治性实体瘤的临床研究

目的 研究^32P胶体或微球治疗难治性实体瘤的疗效。方法 30例难治性实体瘤患者经动脉内介入，手术野直视或在CT引导下经皮注入瘤体内部，接受^32P胶体或微球（259～685MBq）治疗，通过γ照相机、X线平片及CT来观察抑瘤率、副作用及生存期。结果 瘤体内注射^32P制剂后肿瘤生长明显受到抑制。患者的平均生存期为33个月，抑瘤率为96．6％，完全抑制16例占53．3％，部分抑制13例占43．3％。其中1例右叶肝癌患者已带瘤生存至今94月。仅1例治疗无效，治疗后出现放射性肺显影、肝功能衰竭死亡。未出现其他明显副作用。病理检查结果表明，瘤体高度纤维化，内见坏死区，外层形成完整包膜。结论 ^32P胶体或微球是放射性核素治疗难治性实体瘤的理想药物。合理选择适应证和给药方法能进一步提高临床疗效。     

低磁场MRI诊断脊髓内肿瘤的价值

目的: 探讨低磁场MRI诊断脊髓内肿瘤的价值和误诊原因.材料和方法: 对34 例手术和病理证实的髓内肿瘤进行回顾性分析.结果: 室管膜瘤20例, 星形细胞瘤11例, 脂肪瘤2例,血管母细胞瘤1 例,32例肿瘤MRI表现为T1WI等或低信号,T2WI高信号,2例脂肪瘤T1WI和T2WI均为脂肪信号.注射Gd-DTPA后室管膜瘤实性部分呈均匀明显增强 "腊肠样"(12例),星形细胞瘤散在斑片状增强(6例),误诊3例,包括2例多发性硬化、1例急性脊髓炎.结论: 低磁场MRI可为脊髓内肿瘤的早期诊断提供较准确的影像学依据.     

经皮瘤内注射长春瑞滨碘油乳剂治疗兔VX2瘤的实验研究

目的 探讨经皮穿刺瘤内注射长春瑞滨碘油乳剂治疗兔VX2肿瘤的疗效.方法 建立18只兔VX2肿瘤模型,随机分为3组:长春瑞滨碘油乳剂组8只(A组),单纯长春瑞滨溶液组8只(B组),空白对照组2只(C组).在超声引导下经皮瘤内注药后的第4天行肿瘤超声造影,计算超声造影及大体标本的肿瘤坏死率,并行肿瘤组织病理检查.结果 A、B、C3组的超声造影肿瘤肿瘤坏死率分别为64.7％、29.8％、1.7％,大体肿瘤坏死率分别为57.6％、28.2％、1.6％.A组超声造影见肿瘤大部分无增强,病理检查见肿瘤广泛坏死.结论 经皮瘤内注射长春瑞滨碘油乳剂治疗兔VX2肿瘤具有良好疗效.     

32P胶体致人胰腺癌Pc-3移植瘤细胞凋亡及其相关基因表达的研究

目的 观察低剂量^3-P胶体瘤体内注射诱导裸鼠人胰腺癌Pc-3移植瘤细胞凋亡的生物学效应、相关基因的表达及其可能的作用机理。方法建立：BALB／c裸鼠人胰腺癌Pc-3移植瘤动物模型，分别向30只荷瘤鼠瘤块中心注射不同剂量(0．37、0．74、1．48、2．96和5．92MBq)的^32P胶体溶液，对照组注射等体积冷胶体。于注射后24h取出瘤块；通过流式细胞仪、透射电镜及免疫组织化学检测等方法，研究肿瘤组织的细胞凋亡率、细胞坏死率、细胞超微结构改变及Apo2．7、Caspase-3、bcl-2、box相关基因的表达。结果 0．74、1．48和2．96MBq组瘤体内注射后电镜下可见典型的细胞凋亡表现，5．92MBq组细胞则以大量坏死为主。辐射诱导凋亡过程中，bcl-2／bax比值下调，Apoa2.7、Caspase-3蛋白表达均明显增加。结论 ^32P胶体瘤体注射可诱导荷瘤裸鼠人胰腺癌Pc-3肿瘤细胞凋亡；Aao2．7、Caspase-3、bcl-2及bax蛋白参与调控辐射诱导细胞凋亡过程。     

兔VX2肝癌MRI征象与病理对照研究

目的探讨新西兰兔VX2肝癌MRI征象的病理学基础。方法移植法建立新西兰兔VX2肝癌模型20只共32个瘤灶。模型建立后2~4周,全部兔肝癌模型行肝脏MRI平扫,10只兔肝癌模型(包括15个瘤灶)加做MRI增强扫描。MRI检查完成后,留取肿瘤最大横截面标本,行VX2肝癌MRI征象与病理学对照研究。结果种植瘤成活率为100%。T2WI 6个瘤灶呈均匀稍高信号,其余26个瘤灶显示特征性瘤内异常信号,其中"结中结征"5个瘤灶、"靶环征"7个瘤灶、"点彩征"14个瘤灶。对照研究证实此种瘤内异常信号病理基础为不同结构类型的坏死肿瘤组织。增强后肿瘤环形强化,轻微强化6个瘤灶,中等程度强化7个瘤灶,明显强化2个瘤灶,光镜下轻微强化者强化肿瘤组织有大量点状坏死区,明显强化者瘤内血窦明显扩张。结论MRT2WI可评价坏死肿瘤组织结构类型,兔VX2肝癌肿瘤强化程度与肿瘤内血窦扩张程度及瘤内点状坏死数量有关。     

椎管内神经鞘瘤的MRI诊断(附15例分析)

目的评价MRI对椎管内神经鞘瘤的诊断价值。材料与方法15例经手术、病理证实的病例,回顾性分析其MRI表现。结果椎管内神经鞘瘤MRI表现椎管内圆形、卵圆形或不规则形肿块,部分呈哑铃状;肿瘤在T1加权像上呈低信号或略低信号,T2加权像呈高信号,注射GD-DTPA后肿瘤呈均匀性强化,液化坏死区不强化,肿瘤边界清晰。结论MRI对椎管内神经鞘瘤具有独特的诊断优势。     

32P-磷酸铬间质给药在荷人胰腺癌裸鼠的体内生物学分布及形态学表现

目的 研究^32P-磷酸铬(^32P胶体)瘤体间质给药治疗BALB／c—nu／nu裸鼠荷人胰腺癌(Pc-3)移植瘤时在体内相应组织中的分布、药代动力学特点及全身毒性反应。方法 51只荷瘤裸鼠，经瘤体给予不同剂量^32P胶体或尾静脉给药，分批处死，动态观察^32P胶体在裸鼠体内放射性分布和组织器官形态学表现，观察体重变化和计数WBC和PLT，测量瘤体表面放射性计数率。结果 ^32P胶体瘤体间质注射后其放射性计数率明显高于其他器官组织，器官组织放射性计数率瘤体给药明显低于尾静脉给药。增体给药有效半减期为13d。形态学检查显示给药后大部分Pc-3细胞被破坏，并出现分化较好的瘤细胞；肝、脾、肺及淋巴结等重要器官组织的辐射损伤为可逆性．未见明显骨髓抑制现象。结论 ^32P胶体瘤体间质给药是治疗胰腺癌安全、简便、有效的核素介入疗法。     

Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.

The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. METHODS: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. CONCLUSION: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.     

Properties of [(111)In]-labeled HIV-1 tat peptide radioimmunoconjugates in tumor-bearing mice following intravenous or intratumoral injection

INTRODUCTION: Our objective was to evaluate the tumor and normal tissue distribution and nuclear importation properties of [(111)In]-mouse IgG (mIgG) conjugated to tat peptides (GRKKRRQRRRPPQGYG) in athymic mice with subcutaneous BT-474 human breast cancer xenografts. METHODS: Tumor and normal tissue uptake was compared after intravenous (iv) or intratumoral injection of [(111)In]-mIgG-tat and [(111)In]-mIgG. Area under the curve (AUC) was estimated for blood, liver, spleen, kidneys and tumor. Nuclear localization was measured by subcellular fractionation and estimated by microdosimetry. Imaging studies were performed with a gamma-camera. RESULTS: [(111)In]-mIgG-tat was eliminated from the blood and normal tissues two- to threefold more rapidly after iv injection than [(111)In]-mIgG. Tumor uptake was 4-5% injected dose per gram (%ID/g). Tumor radioactivity after intratumoral injection was initially very high (146-154 %ID/g), but declined 12- to 14-fold by 144 h postinjection. There was greater retention of [(111)In]-mIgG-tat in BT-474 tumors after intratumoral than iv injection, and the AUC (610+/-157 %ID h) was threefold greater than for intratumorally injected [(111)In]-mIgG (200+/-37 %ID h). Tat peptides increased nuclear localization of [(111)In]-mIgG after iv injection in tumor, kidney and liver cells, but only in tumor cells after intratumoral injection. Tumors were not imaged after iv administration but were predominant with intratumorally injected [(111)In]-mIgG and [(111)In]-mIgG-tat. Estimated radiation doses to the nucleus of tumor cells from intratumoral [(111)In]-mIgG-tat were 2.8x10(3) mGy/MBq and were 15-fold higher than for iv injection. CONCLUSION: [(111)In]-labeled tat immunoconjugates may have potential for imaging intracellular epitopes or localized Auger electron radiotherapy of tumors.     

Preclinical pharmacokinetic, biodistribution, toxicology, and dosimetry studies of 111In-DTPA-human epidermal growth factor: an auger electron-emitting radiotherapeutic agent for epidermal growth factor receptor-positive breast cancer.

Our objective was to evaluate the pharmacokinetics, normal tissue distribution, radiation dosimetry, and toxicology of human epidermal growth factor (hEGF) labeled with (111)In ((111)In-diethylenetriaminepentaacetic acid [DTPA]-hEGF) in mice and rabbits. METHODS: (111)In-DTPA-hEGF (3.6 MBq; 1.3 or 13 microg) was administered intravenously to BALB/c mice. The blood concentration-time data were fitted to a 3-compartment model. Acute toxicity was studied with female BALB/c mice at 42 times the maximum planned human dose (MBq/kg) or with New Zealand White rabbits at 1 times the maximum planned human dose (MBq/kg) for a phase I clinical trial. Toxicity was evaluated by monitoring body weight, by determination of hematology and clinical biochemistry parameters, and by morphologic examination of tissues. Radiation dosimetry projections in humans were estimated on the basis of the residence times in mice by use of the OLINDA version 1.0 computer program. RESULTS: The largest amounts of radioactivity were taken up by the liver (41.3 +/- 7.8 [mean +/- SD] percentage injected dose [%ID] at 1 h after injection and decreasing to 4.9 +/- 0.3 %ID at 72 h after injection) and kidneys (18.6 +/- 0.8 %ID at 1 h and decreasing to 4.5 +/- 0.2 %ID at 72 h after injection). (111)In-DTPA-hEGF was cleared rapidly from the blood, with a half-life at alpha-phase of 2.7-6.2 min and a half-life at beta-phase of 24.0-36.3 min. The half-life of the long terminal phase could not be accurately determined. The volume of distribution of the central compartment was 340-375 mL/kg, and the volume of distribution at steady state was 430-685 mL/kg. There was no significant difference in the ratio of body weight at 15 d to pretreatment weight for mice administered (111)In-DTPA-hEGF (1.02 +/- 0.01) and mice administered unlabeled DTPA-hEGF (1.01 +/- 0.01). Erythrocyte, leukocyte, and platelet counts and serum alanine aminotransferase and creatinine levels remained in the normal ranges. No morphologic changes were observed by light microscopy in any of 19 tissues sampled. Minor morphologic changes in the liver were observed by electron microscopy. The projected whole-body dose in humans was 0.19 mSv.MBq(-1). The projected doses to the liver, kidneys, and lower large intestine were 0.76, 1.82, and 1.12 mSv.MBq(-1), respectively. CONCLUSION: (111)In-DTPA-hEGF was safely administered to mice and rabbits at multiples of the maximum dose planned for a phase I trial in breast cancer patients.     

In-111-labeled liposomes: dosimetry and tumor depiction

Neutral phospholipid vesicles (liposomes) were loaded with 0.5 mCi (18.5 MBq) indium-111 and administered to 24 patients with various types of cancer. The median diameter of the liposomes was 77 nm, and lipid dose was 0.78-6.25 mg/kg. Scans obtained 24 and 48 hours after injection of In-111 liposomes showed gradual blood clearance with homogeneous uptake in the normal liver and spleen. Dosimetric estimates for these organs were 2.3 +/- 1.1 and 2.3 +/- 1.4 rad (.02 +/- .01 Gy), respectively, with a whole-body estimate of 0.28 rad (.003 Gy). Radiation dose did not correlate with lipid dose. Total renal excretion of In-111 was less than 2% of the injected dose in all but two patients. Transient eosinophilia occurred in two patients. Tumor was seen in the scans of 22 of 24 patients (unbinded readings). In-111-labeled liposomes may enable the demonstration of suspected or unsuspected sites of tumor.     

~(131)Ⅰ-HpD在小鼠体内的吸收、分布和排泄

血卟啉衍生物（即HpD，定位标记为131I-HpD），经小鼠尾静脉注射后，血药浓度下降较快，全身分布迅速广泛，24至32小时变化较为平缓，32小时后几无变化。肺、脾、肝分布较多，肌肉最少，其它组织介于中间，8小时后血液、甲状腺、肺、肝、大腿肌肉等组织呈下降趋势，而肿瘤组织分布相对较多。与其它组织（肺肝除外）相比，具有相对选择性吸收和潴留作用，这种作用在24小时后较为明显。该药72小时内粪排量（57．5％）大于尿排量（42．5％）。血中放射性一时间曲线符合开放二室模型。     

32P-磷酸铬-聚L乳酸粒子组织间植入对犬长期毒性研究

目的 探讨³²P-磷酸铬-聚L乳酸粒子(³²P-CP-PLLA)间质植入比格犬的安全性和毒性。方法 30只比格犬,随机分成不同药物(³²P-CP-PLLA和胶体³²P-CP)、剂量(185、370和740 MBq)和部位(肝脏和臀大肌)10组(n=3)。术后定期称体重,检测实验室指标,测量血液、排泄物放射性计数率值,动态γ显像和组织形态学观察。结果 γ显像示胶体肝脏组全肝显影,放射性不均匀分布,余组局部放射性持续浓聚,肝脏未见显影。肝内注射胶体³²P-CP 471.67 MBq/m²,全肝吸收剂量为31 Gy,无肝功能损伤;注射794.28 MBq/m²,全肝吸收剂量为56 Gy,有较强的肝毒性及全身毒副作用。肝内植入1588.89 MBq/m²的³²P-CP-PLLA粒子,植入区肝组织的吸收剂量为89.83~178.68 Gy,未见肝功能受损。肝脏胶体370 MBq组分别于23、29和45 d死亡肝纤维化5项全程均值明显高于其他各组。有效半减期:³²P-CP-PLLA平均为11.78 d;³²P-CP肝脏组为6.82 d,肌肉组为8.73 d。组织学表现:肝脏胶体370 MBq组4周内见肝细胞中、重度肝细胞损伤,4~6周出现肝细胞坏死及增生;其余各组4周内见轻~中度肝细胞水肿,8周后未见异常。肌肉给药各组主要表现为横纹肌细胞一过性水肿变性。 血液中放射性计数率值粒子组随时间呈现锯齿状缓慢递减,胶体组呈指数下降。结论 ³²P-CP-PLLA粒子具有在植入部位不迁移,可体内降解,无明显毒副作用等优良特性,适治于不同血供的实体肿瘤。比格犬肝脏能接受³²P-CP致死剂量2倍活度的放射性粒子的辐射。     

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer — dosimetric and biokinetic aspects

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (¹¹¹In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45±0.24×10^–3% ID/g in primary tumours and 0.52±0.20×l0^–3% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm³. The radioactivity half-lives in the tumours were 30±7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that¹¹¹In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using^114m-In-labelled BLMC.     

Pemetrexed improves tumor selectivity of 111In-DTPA-folate in mice with folate receptor-positive ovarian cancer

Folate-based radiopharmaceuticals can be used as imaging agents and for potential radiotherapy of folate receptor (FR)-positive malignant tissue (e.g., ovarian carcinomas). However, substantial FR expression in the kidneys results in undesired renal retention of radioactivity. Recently, we found that the preinjection of an antifolate significantly improved tumor selectivity of organometallic 99mTc-radiofolates in mice. The aim of this study was to corroborate the effect of pemetrexed with the clinically tested 111In-DTPA-folate (DTPA is diethylenetriaminepentaacetic acid) in a human ovarian cancer xenografted mouse model. METHODS: In vivo studies were performed in female athymic nude mice bearing subcutaneous FR-positive ovarian tumors (IGROV-1 and SKOV-3) or metastases (after intraperitoneal SKOV-3 cell inoculation). Biodistribution studies were performed 1, 4, and 24 h after administration of 111In-DTPA-folate (0.7 MBq/mouse, 0.35 mug) with or without preinjection of pemetrexed (PMX, 400 microg) 1 h before the radiofolate. Images were acquired with a high-resolution, high-sensitivity SPECT/CT camera, 4 and 24 h after injection of the radiotracer (30-50 MBq/mouse, 4.5-10 microg). RESULTS: In biodistribution studies the tumor uptake of 111In-DTPA-folate (IGROV-1: 9.79 +/- 3.21 %ID/g [percentage injected dose per gram]; SKOV-3: 7.57 +/- 0.61 %ID/g, 4 h after injection) was high and retained over the time of investigation. However, considerable retention of radioactivity was found in kidneys (85-105 %ID/g, 4 h after injection), resulting in unfavorably low tumor-to-kidney ratios ( approximately 0.10). Preinjection of PMX resulted in a significant reduction of renal uptake (20%-30% of control values, P < 0.03) at all time points after injection of 111In-DTPA-folate, whereas the tumor uptake was retained. Thus, the tumor-to-kidney ratio was significantly increased to approximately 0.50. SPECT/CT images confirmed the superior tumor-to-background ratio in mice injected with PMX. These findings were particularly evident in mice with SKOV-3 metastases that could be visualized only when 111In-DTPA-folate was administered in combination with PMX. CONCLUSION: The application of PMX resulted in a significant reduction of undesired radioactivity accumulation in kidneys, whereas the tumor uptake remained unaffected. These observations suggest a general validity of the reducing effect of PMX on the uptake of radiofolates in kidneys. Our findings will lead the way toward the development of folate-based radiotherapy.     

Comparison of immunoscintigraphy, efficacy, and toxicity of conventional and pretargeted radioimmunotherapy in CD20-expressing human lymphoma xenografts.

Pretargeted radioimmunotherapy (RIT) using streptavidin (sAv)-conjugated antibodies before radiolabeled-biotin is a promising approach to improve absorbed dose ratios and achieve high durable remission rates with diminished systemic toxicity. This study compared the immunoscintigraphy, toxicity, and therapeutic efficacy of pretargeted RIT with conventional RIT using an anti-CD20 antibody. METHODS: Athymic mice bearing Ramos human Burkitt's lymphoma xenografts were injected intraperitoneally with a 1F5-sAv conjugate followed 24 h later by a galactosylated, biotinylated clearing agent (CA) and, finally, 3 h later by (111)In- or (90)Y-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin. The comparison groups consisted of mice injected with conventional, directly labeled (111)In- or (90)Y-1F5. RESULTS: Rapid tumor uptake of radioactivity within 2 h was observed with the pretargeting approach, resulting in high-contrast tumor images at 24 h with minimal blood-pool radioactivity. Although conventional radiolabeled antibodies produced clear tumor images at 24 h, a large amount of radioactivity was present in the blood pool. The tumor-to-blood ratio was 3.5:1 with pretargeting compared with 0.4:1 with conventional (111)In-1F5. Pretargeted RIT with 29.6 MBq (800 micro Ci) (90)Y-DOTA-biotin cured 100% of mice with tolerable toxicity, whereas conventional RIT with (90)Y-1F5 at a dose of 14.8 MBq (400 micro Ci) produced no cures, induced profound pancytopenia, and was lethal to all mice. CONCLUSION: These results suggest that anti-CD20 pretargeted RIT may be superior to conventional radiolabeled antibodies in terms of radioimmunoscintigraphy, toxicity, and therapeutic efficacy for treatment of B-cell lymphomas.