Physical aspects of yttrium-90 microsphere therapy for nonresectable hepatic tumors

Administration of yttrium-90 microspheres via the hepatic artery is an attractive approach to selectively deliver therapeutic doses of radiation to liver malignancies. This procedure allows delivering radiation absorbed doses in excess of 100 Gy to the tumors without significant liver toxicity. The microsphere therapy involves different specialties including medical oncology, radiation oncology, nuclear medicine, interventional radiology, medical physics, and radiation safety. We have treated 80 patients with nonresectable hepatic tumors with yttrium-90 microspheres during the past two years on an institutional study protocol. The nominal radiation absorbed dose to the tumor in this study was 150 Gy. Required activity was calculated based on the nominal radiation absorbed dose and patient's liver volume obtained from the CT scan, assuming a uniform distribution of the microspheres within the liver. Microspheres were administered via a catheter placed into the hepatic artery. The actual radiation absorbed doses to tumors and normal liver tissue were calculated retrospectively based on the patient's 99mTc-MAA study and CT scans. As expected, the activity uptake within the liver was found to be highly nonuniform and multifold tumor to nontumor uptake was observed. A partition model was used to calculate the radiation absorbed dose within each region. For a typical patient the calculated radiation absorbed doses to the tumor and liver were 402 and 118 Gy, respectively. The radiation safety procedure involves confinement of the source and proper disposal of the contaminated materials. The average exposure rates at 1 m from the patients and on contact just anterior to the liver were 6 and 135 uSv/h, respectively. The special physics and dosimetry protocol developed for this procedure is presented.     

大鼠种植性CBRH-7919肝癌模型的MRI、数字减影血管造影及病理学表现

背景：大鼠种植性CBRH-7919肝癌模型是肝癌实验性治疗和影像学诊断研究重要的工具,但模型建立后如何对模型进行检测和验证鲜有报道。 目的：通过彩色超声、MRI及肝动脉血管数字减影血管造影检查的方法来检测和验证Wistar大鼠种植性CBRH-7919肝癌模型,并探讨大鼠种植性CBRH-7919肝癌模型的影像学及病理表现。 方法：CBRH-7919大鼠肝癌细胞瘤株接种裸鼠双侧肩胛部皮下,再将生成的肿瘤组织在开腹直视下移植接种于成年Wistar大鼠肝脏内,建立大鼠种植性CBRH-7919肝癌模型。模型建立4周后用彩超检查、筛选建模成功的Wistar大鼠进行MRI检查、肝动脉血管数字减影血管造影及病理学检查。 结果与结论：在建模成功的35只大鼠中,超声检查发现37个结节,MRI检查发现肝脏内共41个结节,较超声增加4个;最小的结节约3 mm,最大约8 mm。MRI扫描显示T1WI表现为低信号,T2WI及脂肪抑制序列表现高信号。肝动脉血管数字减影血管造影均表现由肝动脉供血的富血供结节。光学显微镜下观察可见肿瘤细胞呈巢状或条块状排列,周围伴行多条血管,肿瘤细胞体积大小不一致,核大而浓染,细胞质少,异型性明显。结果表明彩超和核磁共振扫描是大鼠肝癌检查简单而有效的方法,肝动脉血管数字减影血管造影可以了解肿块的供血动脉及其血供情况。通过对Wistar大鼠种植性肝癌模型的MRI及肝动脉血管数字减影血管造影表现能反映肿瘤的病理形态学和生物学行为改变。     

Numerical simulation of the hepatic circulation

Availability of donor livers and the relatively short preservation time limit the success of liver transplantation. The use of hypothermic machine perfusion could pave the way for expansion of the donor pool. To better define optimal settings of such a device, the feasibility of using a numerical simulation model of the hepatic circulation is determined. Hemodynamics in the hepatic arterial, portal venous and hepatic venous compartments of the hepatic vascular tree was modelled using an electrical analogue. Calculated pressure and flow profiles throughout the liver were in accordance with physiologic profiles in the total circulatory system. Comparison of calculated flow values with normal control values showed a discrepancy that was explained by inaccurate diameter input data. Until more precise methods for determining vascular dimensions become available, redefining vessel diameter makes the simulation model perfectly suitable for predicting influences of temperature and/or viscosity on hepatic hemodynamics and is thereby an excellent tool in defining optimal settings for our hypothermic liver perfusion system.     

利用微血管铸型技术研究肝外胆管动脉的分布特征

目的　统计分析肝外胆管的血供来源和分布以及在十二指肠上段胆管的吻合动脉链之间的多环形血管网,为胆管外科手术提供临床解剖学理论依据。 方法　以丙烯酸树脂为动脉填充剂灌注6例肝外胆管动脉制备铸型标本,使用photoshop测量法测量微小血管内径,观测和分析肝外胆管的血供来源和分布情况。 结果　肝固有动脉左、右支在肝总管上方存在弓型交通支,十二指肠上段胆管左右边缘的吻合动脉链间有丰富的横向动脉,吻合动脉链的供血约53%来自下方,来自上方的约占46%,1%来自中段肝固有动脉。通过对每条横向动脉中部的内径和两侧起始部的内径测量,发现肝总管中段和上段的横向动脉较粗,中部的平均内径分别为（0.26±0.02）mm和（0.24±0.04）mm,与两侧的内径比也比较大,上段比值最大,为1.09,中段其次,为1,下段中部的平均内径为（0.14±0.03）mm;与两侧的内径比值为0.74。 结论　肝外胆管上、下方的血供来源比例相对均衡;肝外胆管手术应尽可能于动脉吻合相对较少的胆总管十二指肠上段和血管相对较细小肝总管下部做纵行小切口,以降低肝外胆管血供的损伤;肝总管段的血供丰富,支持现行原位肝移植离断部位在胆囊管汇合处上方的主张。     

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy

The microscopic distribution of microspheres in human liver following hepatic infusion of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 microm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.     

Impact of Fluid–Structure Interaction on Direct Tumor-Targeting in a Representative Hepatic Artery System

Direct targeting of solid tumors with chemotherapeutic drugs and/or radioactive microspheres can be a treatment option which minimizes side-effects and reduces cost. Briefly, computational analysis generates particle release maps (PRMs) which visually link upstream particle injection regions in the main artery with associated exit branches, some connected to tumors. The overall goal is to compute patient-specific PRMs realistically, accurately, and cost-effectively, which determines the suitable radial placement of a micro-catheter for optimal particle injection. Focusing in this paper on new steps towards realism and accuracy, the impact of fluid–structure interaction on direct drug-targeting is evaluated, using a representative hepatic artery system with liver tumor as a test bed. Specifically, the effect of arterial wall motion was demonstrated by modeling a two-way fluid–structure interaction analysis with Lagrangian particle tracking in the bifurcating arterial system. Clearly, rapid computational evaluation of optimal catheter location for tumor-targeting in a clinical application is very important. Hence, rigid-wall cases were also compared to the flexible scenario to establish whether PRMs generated when based on simplifying assumptions could provide adequate guidance towards ideal catheter placement. It was found that the best rigid (i.e., time-averaged) geometry is the physiological one that occurs during the diastolic targeting interval.     

基于三维可视化技术对巨块型肝癌肝动脉血管分布规律的分析与研究

目的:基于三维可视化技术对CT数据处理、分析,研究巨块型肝癌肝动脉的分布规律。方法:收集93例正常人（正常组）和93例巨块型肝癌患者（肝癌组）CT数据,利用IPS软件三维重建,研究正常组与肝癌组肝动脉的差异以分析其变化规律。结果:肝癌组肝固有动脉、肝固有动脉左支、肝固有动脉右支和肝中动脉起始处血管平均直径均比正常组相应部位血管管径增粗,差异有统计学意义（P<0.05）;肝癌组肝固有动脉右支血管分支多于正常组动脉血管分支,差异有统计学意义（P<0.05）;巨块型肝癌位于肝左叶者,与正常组对比有76.9%膈动脉分支包绕/嵌入肝癌肿瘤,可认为其为肝癌供血的新生血管;巨块型肝癌位于肝右叶和肝中部者,新生血管呈球状包绕肝癌。结论:巨块型肝癌肝动脉的变化规律可从血管直径、分支及新生血管位置研究,为临床精准介入治疗提供指导价值。     

Targeting microspheres and cells to polyethylene glycol-modified biological surfaces

It has previously been demonstrated that damaged arterial tissue can be acutely modified with protein-reactive polyethylene glycol (PEG) to block undesirable platelet deposition. This concept might be expanded by employing PEG-biotin and its strong interaction with avidin for site-specific targeted delivery. Toward this end, cultured endothelial cells (ECs) were surface modified with PEG-biotin and the available biotin was quantified with flow cytometry. NeutrAvidin-coated microspheres and PEG-biotin modified ECs with NeutrAvidin as a bridging molecule were delivered under arterial shear stress to PEG-biotin modified ECs on a coverslip as well as scrape-damaged bovine carotid arteries. After incubation with a 10 mM solution for 1 min, 8 x 10(7) PEG-biotin molecules/EC were found and persisted for up to 120 h. Perfused microspheres adhered to NHS-PEG-biotin treated bovine carotid arteries with 60 +/- 16 microspheres/mm(2) versus 11 +/- 4 microspheres/mm(2) for control arteries (p < 0.015). Similarly, 22 +/- 5 targeted ECs/mm(2) adhered to NHS-PEG-biotin treated bovine carotid arteries versus 6 +/- 2 ECs/mm(2) for control arteries (p < 0.01). The targeting strategy demonstrated here might ultimately find application for drug delivery, gene therapy, or cell therapy where localization to specific labeled vascular regions is desired following catheter-based or surgical procedures.     

块状型肝癌化疗栓塞后血液动力学改变的临床意义

目的：探讨块状型肝癌化疗栓塞（TACE）后肝内血管血流动力学改变的临床意义。方法：对51例肝右叶块状型肝癌患者行TACE治疗,采用Seldinger技术将微导管超选择至肿瘤的供血动脉,经栓塞-化疗-再栓塞后再次行DSA造影检查。TACE术前、术后两次造影条件相同,观察肿瘤区和非肿瘤区血流动力学变化。结果：51例中,肿瘤组织内动脉有增生或显著增生的血管网43例（84．3％）,主瘤栓塞后DSA检出1～3个大小不等的次瘤34例（66．7％）。TACE后,肿瘤区血管密度减小、非肿瘤区血管密度增大,肝固有动脉、肝右动脉和胃十二指肠动脉管径增粗、血流量增多。结论：TACE后肝肿瘤区血流速度减慢,有利于化疗药物和栓塞剂的存留。主瘤栓塞后次瘤的发现,对于手术治疗的取舍有重要的参考价值。观察TACE前后血流动力学的变化为肿瘤综合治疗方案的拟定提供了有价值的临床信息。     

Hepatic arterial perfusion regulates portal venous flow between hepatic sinusoids and intrahepatic shunts in the normal rat liver in vitro

Intrahepatic shunts regulate portal venous pressure during periods of acute portal hypertension when the transhepatic portal resistance is momentarily increased in the normal rat liver in vivo. Hepatic arterial inflow may also increase the transhepatic portal resistance and activate intrahepatic shunts. In the present study, the transhepatic portal resistance and the activity of intra-hepatic shunts were measured in vitro and the point of confluence between the hepatic artery and portal vein in the rat determined. Livers of male Sprague-Dawley rats were single-pass, dual-perfused in vitro. Total cessation or diversion of the hepatic arterial inflow to the portal venous vasculature, whilst maintaining total hepatic perfusate flow, decreased intrasinusoidal pressure, increased transhepatic portal venous resistance and opened the portal venous intrahepatic shunts in a manner similar to intraportal injection of 15-microm diameter microspheres. Injections of the microspheres into the hepatic arterial circulation increased hepatic arterial pressure dramatically, consistent with complete occlusion of the arterial vasculature. The intrahepatic shunts are located at a pre-sinusoidal level because no increases were detected in hepatic arterial pressure following intraportal injection of microspheres. The hepatic arterial vasculature, unlike the portal supply, does not possess a collateral shunt circulation and coalesces with the portal vein at an intrasinusoidal location     

Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System

Combating liver tumors via yttrium-90 (⁹⁰Y) radioembolization is a viable treatment option of nonresectable liver tumors. Employing clinical ⁹⁰Y microparticles (i.e., SIR-Spheres^® and TheraSpheres^®) in a computational model of a representative hepatic artery system, laminar transient 3D particle-hemodynamics were simulated. Specifically, optimal particle release positions in the right hepatic (parent) artery as well as the best temporal release window were determined for the microspheres to exit specific outlet daughter vessels, potentially connected to liver tumors. The results illustrate the influence of a curved geometry on the velocity field and the particle trajectory dependence on the spatial and temporal particle injection conditions. The differing physical particle characteristics of the SIR-Spheres^® and the TheraSpheres^® had a subtle impact on particle trajectories in the decelerating portion of the arterial pulse, i.e., when the inertial forces on the particles are weaker. Conversely, particle characteristics and inelastic wall collisions had little effect on particles released during the accelerating phase of the arterial pulse, i.e., both types of microspheres followed organized paths to predetermined outlets. Such results begin paving the way towards directing 100% of the released microspheres to specific daughter vessels (e.g., those connected to tumors) under transient flow conditions in realistic geometries via a novel drug-particle targeting methodology.     

Dose calculation of 142Pr microspheres as a potential treatment for arteriovenous malformations

Arteriovenous malformation (AVM), especially cryptic AVM, can cause highly variable cerebral neurological defects. Injection of 142Pr microspheres into arteries feeding an AVM in order to simulate radio-embolism has been proposed as a novel treatment method. To investigate optimization of radiation dose to the clinically important arterial wall area, preliminary dosimetric studies have been performed. Monte Carlo calculations were performed for simulated arteries filled with microspheres packed by random packing. Arterial radii from 0.05 mm to 3 mm and microsphere radii from 0.01 mm to 0.7 mm were used in the simulation. For constant arterial size, dose varied significantly with microspheres radius. Inter-arterial effect was also simulated using simplified geometry. For the inter-arterial sites, the dose rate was calculated between two arteries of the same size parallel to each other. The dose increased significantly for large arteries (>1 mm radius) filled with large microspheres (>0.3 mm radius). The dose increase between small arteries (<0.3 mm radius) was not as significant as that between large arteries. Overall results indicate that arterial size and microsphere size significantly affect the dose profile. This factor should be taken into account in future clinical applications.     

Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods

The purpose of this study was to evaluate the antitumor efficacy and local drug distribution from doxorubicin-containing poly(D,L-lactide-co-glycolide) (PLGA) implants for intratumoral treatment of liver cancer in a rabbit model. Cylindrical polymer millirods (length 8 mm, diameter 1.5 mm) were produced using 65% PLGA, 21.5% NaCl, and 13.5% doxorubicin. These implants were placed in the center of VX2 liver tumors (n = 16, 8 mm in diameter) in rabbits. Tumors were removed 4 and 8 days after millirod implantation, and antitumor efficacy was assessed using tumor size measurements, tumor histology, and fluorescent measurement of drug distribution. The treated tumors were smaller than the untreated controls on both day 4 (0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm(2), p = 0.048) and day 8 (0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm(2), p = 0.025). Drug distribution profiles demonstrated high doxorubicin concentrations (>1000 microg/g) at the tumor core at both time points and drug penetration distances of 2.8 and 1.3 mm on day 4 and 8, respectively. Histological examination confirmed necrosis throughout the tumor tissue. Biodegradable polymer millirods successfully treated the primary tumor mass by providing high doxorubicin concentrations to the tumor tissue over an eight day period.     

Focal hepatic steatosis surrounding a metastatic insulinoma

Reported herein is a case of focal hepatic steatosis surrounding a metastatic insulinoma in the liver of a 69-year-old woman. The patient complained of losing consciousness after meals, and hypoglycemia and hyperinsulinemia were confirmed. On CT and abdominal angiography a mass, 1 cm in diameter, was seen in the tail of the pancreas. In the early phase of dynamic CT a mass, 5 mm in diameter, was seen in the liver. In the late phase this mass appeared to be 3 cm in diameter. An arterial calcium stimulation/venous sampling test showed insulin levels after calcium injections in the hepatic artery to be extremely high. Thus, the liver tumor was diagnosed as a metastatic insulinoma, and distal pancreatectomy and partial resection of the liver were performed. The pancreatic tumor cells were immunohistochemically positive for insulin. The liver tumor was pale yellow. A white area surrounded the tumor. Histologically, the liver tumor was an insulinoma and the white area was focal fatty change of the liver. High insulin levels are said to inhibit oxidation of free fatty acids into triglycerides, causing free fatty acids to accumulate in hepatocytes. Focal hepatic steatosis caused by the local effects of insulin can present as a focal rim surrounding a metastatic insulinoma.     

Anticancer gelatin microspheres with multiple functions.

Biodegradable, hydrophilic gelatin microspheres (GM) with an average diameter of 70 microns were prepared by cross-linking gelatin with glutaraldehyde for hepatic intra-arterial infusion. An anticancer agent, mitomycin C (MMC), together with a radioisotope, 131I, were bound to the GM for chemotherapy and local internal radiotherapy. The 131I-labelled MMC-GM (131I-MMC-GM) could accumulate in the specific site and embolize the hepatic arteries after the hepatic intra-arterial infusion, while it caused various effects to the liver cells. The 131I-MMC-GM remained within the hepatic arteries for at least one month. In vitro release of drugs from the GM was also quantified using a dynamic dialysis method.     

肝动脉解剖变异的DSA研究

目的:进一步探讨肝动脉解剖变异的种类及分型,结合文献提出肝动脉变异的新分型。方法:回顾分析1000例因肝脏疾病而行DSA检查患者肝动脉的起源、走行、分布情况,并分别统计其变异类型和发生率。结果:1000例肝动脉造影中,正常型占72.7%(727例)。肝动脉变异占27.3%(273例)。273例肝动脉变异中肝总动脉分叉变异占5.4%(54例);肝动脉起源变异占21.4%(214例);肝动脉分叉 起源变异占0.5%(5例)。结论:肝动脉解剖变异的种类具有多样性、复杂性。结合文献和本研究结果提出肝动脉解剖变异的新分型:正常型、肝总动脉分叉变异、肝动脉起源变异、肝总动脉分叉变异合并肝动脉起源变异、多种变异共存五大类,共50余种。     

Celiac trunk compression by arcuate ligament and living-related liver transplantation: a two-step strategy for flow-induced enlargement of donor hepatic artery

The median arcuate ligament is a tendinous arch joining the two medial borders of the diaphragm crura together. In 10-50% of subjects it is responsible for significant angiographic celiac trunk compression. In severe cases, a decrease in hepatic arterial blood flow with subsequent artery caliber reduction and reverse vascularization via the gastroduodenal artery is present. In liver transplantation, small-caliber hepatic arteries are higher risk factors for hepatic arterial thrombosis and frequent graft loss. We report a case of celiac trunk compression in a living-related donor and the two-step strategy we developed to perform a safer liver transplantation via flow-induced enlargement of the donor hepatic artery. A 29-year-old father was selected as a living-related liver donor for his 4-year-old daughter. Angiography revealed celiac trunk compression by the median arcuate ligament with reverse vascularization of the middle hepatic artery via the gastroduodenal artery, a proper hepatic artery 2 mm in diameter irrigating the left lateral segment exclusively, and a right hepatic artery irrigating the right lobe and segment 4. First-step division of the median arcuate ligament and gastroduodenal artery ligation were performed. Repeat angiography at the third week showed a 50% enlargement of the middle hepatic artery (3 mm). Second-step left lobectomy was performed at the fifth week. The transplantation was achieved with an arterial anastomosis between the middle hepatic arteries of donor and recipient. This two-step strategy including median arcuate ligament division provided flow-induced enlargement of the donor middle hepatic artery for a safer transplantation with arteries of more suitable calibers.     

胎肝血管的解剖及其移植应用

目的观察胎肝的血管特点,探讨在临床带血管的胎肝移植的血管吻合的选择性。方法6～10个月胎龄的死胎33例于手术放大镜下原位解剖胎肝的附属血管,用直尺、卡尺和分割规测量附属血管的外径和长度。结果6～10个月胎龄的胎肝脐静脉的外径为(3.68±0.48)mm～(5.61±0.87)mm,长度为(36.12±4.58)mm～(50.97±7.68)mm;门静脉的外径为(2.31±0.43)mm～(4.16±0.65)mm,长度为(15.62±2.68)mm～(29.03±4.87)mm;肝固有动脉的外径为(1.67±0.82)mm～(2.32±0.98)mm,长度为(14.96±3.03)mm～(25.58±3.85)mm。脐静脉的外径较门静脉的外径粗(P<0.05);门静脉的外径较肝固有动脉的外径粗(P<0.05)。结论在胎肝移植前先结扎静脉导管,以脐静脉替代门静脉吻合,门静脉替代肝固有动脉吻合,更有利于吻合技术操作和供肝的双重血供,更有利于供肝发挥正常的功能。     

Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model

Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 h. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors.     

Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

Background

Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres^® Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment.

Methods

Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers.

Results

Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging.

Conclusion

Dosesup to99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure.The lowest tumor dose producing a detectable response is 40.1 Gy.The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes.