Hepatic Arterial Injection Research Articles

Hepatic tumor radioembolization in a rat model using radioactive rhenium ( 186Re/ 188Re) glass microspheres

Purpose: The aim of this study was to fully characterize newly developed radioactive rhenium glass microspheres in vivo by determining their biodistribution, stability, antitumor effect, and toxicity after hepatic arterial injection in a syngeneic rat hepatoma model. The dose response of the tumors to increasing amounts of radioactive 186Re and 188Re microspheres was also determined. Methods and Materials: Rhenium glass microspheres were made radioactive by neutron activation and then injected into the hepatic artery of Sprague–Dawley rats containing 1-week-old Novikoff hepatomas. The biodistribution of the radioactivity and tumor growth were determined 1 h and 14 days after injection. Results: Examination of the biodistribution indicated a time-dependent, up to 7-fold increase in Novikoff hepatoma uptake as compared to healthy liver tissue uptake. After 14 days, the average T:L ratio was 1.97. Tumor growth in the rats receiving radioactive microspheres was significantly lower than in the group receiving nonradioactive microspheres (142% vs. 4824%, p = 0.048). Immediately after injection, 0.065% of the injected radioactivity was measured in the thyroid; it decreased to background levels within 24 h. Conclusion: Radioactive rhenium microspheres are effective in diminishing tumor growth without altering hepatic enzyme levels. The microspheres are safe with respect to their radiation dose to healthy tissue and radiation release in vivo and can be directly imaged in the body with a gamma camera. Furthermore, rhenium microspheres have an advantage over pure beta-emitting microspheres in terms of preparation and neutron-activation time. In sum, this novel radiopharmaceutical may provide an innovative and cost-effective approach for the treatment of nonresectable liver cancer.

A simple and accurate mathematical method for calculation of the EC 50

A simple, accurate, and speedy noncomputational technique for the calculation of the EC 50 or any other concentration-related parameter of concentration–effect curves is presented. It avoids the necessity for graph construction or computational curve-fitting programs and allows accurate calculation of the EC 50, where the value falls between two known concentrations The technique has been applied to a concentration–response curve constructed to hepatic arterial (HA) vasoconstrictor responses to HA injections of noradrenaline in an isolated dual-perfused rat liver preparation. EC 50 values calculated by the new technique were compared to those calculated by conventional, established, noncomputational techniques. The new technique is faster, more accurate, and simpler to perform than other established noncomputational techniques used for the calculation of the EC 50 and can be widely applied to many other pharmacological investigations.

肝細胞癌の動脈塞栓療法に用いる塩酸エピルビシン封入ｗ／ｏ／ｗ型エマルションの設計とｉｎ ｖｉｖｏ評価

We developed a novel w/o/w emulsion formulation containing medium-chain triglyceride (MCT) as an oily phase and lomeron 300 as an aqueous phase with functions of embolizing and sustaining drug-release in trans-catheter arterial embolization (TAE) therapy for hepatocellular carcinoma. The various formulations with various kinds of surfactants were applied to the MCT w/o/w emulsion to improve its stability. The most stable w/o/w emulsion was obtained when the mixture of HCO-10 and CO-3 (1 : 1) of 3% in oily phase and HCO-60 of 5% in aqueous phase were formulated. The stability of emulsion was also evaluated by a drug release test with Spin-Biodialyser™ Double-sided for the emulsions encapsulating epirubicin hydrochloride (EPI), doxorubicin hydrochloride (DOX) or Evans blue in an inner aqueous phase. The drug release profiles suggested the sustained drug release property of the emulsions. When normal rats were treated with the hepatic arterial injection of the MCT w/o/w emulsion encapsulating EPI, there was non dysfunction trans aminase of GOT and GPT in normal liver. The increased drug retention in liver after the arterial administration of EPI in a w/o/w emulsion form in rats bearing a hepatic tumor revealed the usefulness of this device for the drug targeting to the hepatic tumor.

Localisation of hepatic vascular resistance sites in the isolated dual-perfused rat liver

The locations of the vascular resistance sites which regulate vascular tone in the hepatic arterial and portal venous vasculatures of the rat liver were identified using a new, in vitro, dual-perfused liver preparation. Twelve livers of male Wistar rats were perfused via the hepatic artery and portal vein at fixed flow and at physiological pressure. Dose-related vasoconstriction to injections or infusions of noradrenaline was measured as transient or sustained increases in perfusion pressure, respectively, in the hepatic arterial and portal venous vasculatures. Direct injections/infusions of noradrenaline refer to those administered into the vasculature from which pressure was recorded, e.g., the effects of hepatic arterial (direct) injections/infusions of noradrenaline upon hepatic arterial perfusion pressure. Indirect injections/infusions of noradrenaline were those administered to the adjacent afferent vasculature, e.g., the effects of portal venous (indirect) injections of noradrenaline upon hepatic arterial perfusion pressure. The converse applies for recordings of portal venous perfusion pressure. The −log( M) ED 50 values to direct (hepatic arterial) and indirect (portal venous) injections in the hepatic artery were 4.25±0.20 and 3.40±0.10, respectively, and were significantly different ( P<0.01, Student's unpaired t-test); the −log( M) ED 50 values to direct (portal venous) and indirect (hepatic arterial) injections in the portal vein were 3.91±0.08 and 3.85±0.11, respectively, and were not significantly different ( P>0.05, Student's unpaired t-test). Similarly, the −log( M) ED 50 values to direct (hepatic arterial) and indirect (portal venous) infusions in the hepatic artery were 5.28±0.11 and 3.75±0.12, respectively, and were significantly different ( P<0.01, Student's unpaired t-test); the −log( M) ED 50 values to direct (portal venous) and indirect (hepatic arterial) infusions in the portal vein were 5.31±0.19 and 5.70±0.16, respectively, and were not significantly different ( P>0.05, Student's unpaired t-test). These results demonstrated that there is little transfer of noradrenaline from the portal venous to the hepatic arterial resistance sites, but significant transfer from the hepatic artery to the portal venous suggesting that; (a) the portal venous resistance sites are located at the sinusoidal or post-sinusoidal level; and (b) the hepatic arterial resistance sites are located at the pre-sinusoidal level.

Lipiodol avidity of neuroendocrine liver metastases

Lipiodol has been shown to concentrate in most hepatocellular carcinomas as well as in some liver metastases, including those of neuroendocrine origin. Our aim was to determine the proportion of neuroendocrine liver metastases that take up lipiodol and to identify tumour characteristics that predict avidity. Avidity was assessed in 12 patients with neuroendocrine liver metastases by performing an abdominal CT scan immediately after selective hepatic arterial injection of 5 ml of unlabelled lipiodol and this was correlated with number and size of lesions as well as angiographic and plain CT scan features. In seven patients the tumours displayed lipiodol avidity (four solitary, three multiple); five patients had non-avid lesions (all multiple). A large dominant liver tumour was the only predictor of avidity (mean diameter of largest lesion 9 cm vs. 3 cm for patients with non-avid tumours: P=0.01). Avidity was not related to vascularity or CT density of lesions. Although this is a small study, it would appear that approximately 50% of neuroendocrine liver metastases selectively concentrate lipiodol, which could have implications for targeted cancer therapy.

Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vascularization of diethylnitrosamine-induced hepatocarcinomas using a computerized tomography scanner approach. The efficacy of gene transfer was then evaluated by three routes of administration: intraportal, selective injection through the hepatic artery and direct injection into the tumor. Diethylnitrosamine-induced hepatocarcinomas had predominantly an arterial blood supply, 67% of the total liver blood supply. Compared with intraportal administration, arterial injection improved gene transfer into tumors whereas that to the non-tumor areas was diminished. In addition, this route of injection allowed the efficient transduction of dysplastic nodules. Diethylnitrosamine-induced hepatocarcinoma in rats is a relevant model for the study of human hepatocarcinoma due to its vascularization. Arterial infusion improved the ratio of transduced tumorous to nontumorous cells and allowed targeting of gene transfer to dysplastic nodules. This will be useful in the design of gene therapy for hepatocarcinoma.

P-1-22 - Acute subdural hematoma associated with aneurysmal subarachnoid hemorrhage

Yttrium 90 radioembolization is a transcatheter therapy for unresectable hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In contrast to the usual method of lobar regional delivery, catheter-directed computed tomographic (CT) angiography was investigated as a potentially useful technique to evaluate the administration of segmental90Y tumor radiation doses superselectively without significantly altering liver function or Child-Pugh classification.Fourteen patients underwent 90Y therapy for unresectable HCC. After standard angiographic placement of a 3-F microcatheter in a segmental hepatic artery supplying the tumor, each patient underwent CT angiography with use of segmental hepatic artery injection of iodinated contrast agent to confirm segmental perfusion and delineate segmental liver volume. 90Y was later injected into the same segmental artery. Target dose was calculated according to infused 90Y activity and targeted hepatic volume with standard lobar volume (before CT angiography) versus segmental liver volume (after CT angiography). The Wilcoxon signed-rank test (α0.05) was used to compare the estimated 90Y dose before CT angiography with the actual 90Y dose after CT angiography, as well as changes in serum bilirubin level and Child-Pugh classification as a result of treatment.The mean estimated tumor dose before CT angiography (SD) was 100 Gy±43 (range, 35–169 Gy). The mean actual tumor dose after CT angiography was 348 Gy±204 (range, 105–857 Gy), which was significantly greater (P < .001). The mean bilirubin level before treatment was 1.0 mg/dL ±0.97 (range, 0.2–4.0 mg/dL), whereas the mean bilirubin level after treatment was 1.3 mg/dL ±0.85 (range, 0.5–3.8 mg/dL). This difference, although statistically significant (P=.03), was not clinically important. Thirteen of 14 patients had no change in Child-Pugh class.CT angiography can be used to delineate the blood supply and volume to a targeted hepatic segment, allowing superselective90Y radioembolization. This approach significantly increases effective 90Y tumor radiation dose without clinically altering liver function or Child-Pugh class.

P-1-25 - Timing of ruptured aneurysm surgery

Yttrium 90 radioembolization is a transcatheter therapy for unresectable hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In contrast to the usual method of lobar regional delivery, catheter-directed computed tomographic (CT) angiography was investigated as a potentially useful technique to evaluate the administration of segmental90Y tumor radiation doses superselectively without significantly altering liver function or Child-Pugh classification.Fourteen patients underwent 90Y therapy for unresectable HCC. After standard angiographic placement of a 3-F microcatheter in a segmental hepatic artery supplying the tumor, each patient underwent CT angiography with use of segmental hepatic artery injection of iodinated contrast agent to confirm segmental perfusion and delineate segmental liver volume. 90Y was later injected into the same segmental artery. Target dose was calculated according to infused 90Y activity and targeted hepatic volume with standard lobar volume (before CT angiography) versus segmental liver volume (after CT angiography). The Wilcoxon signed-rank test (α0.05) was used to compare the estimated 90Y dose before CT angiography with the actual 90Y dose after CT angiography, as well as changes in serum bilirubin level and Child-Pugh classification as a result of treatment.The mean estimated tumor dose before CT angiography (SD) was 100 Gy±43 (range, 35–169 Gy). The mean actual tumor dose after CT angiography was 348 Gy±204 (range, 105–857 Gy), which was significantly greater (P < .001). The mean bilirubin level before treatment was 1.0 mg/dL ±0.97 (range, 0.2–4.0 mg/dL), whereas the mean bilirubin level after treatment was 1.3 mg/dL ±0.85 (range, 0.5–3.8 mg/dL). This difference, although statistically significant (P=.03), was not clinically important. Thirteen of 14 patients had no change in Child-Pugh class.CT angiography can be used to delineate the blood supply and volume to a targeted hepatic segment, allowing superselective90Y radioembolization. This approach significantly increases effective 90Y tumor radiation dose without clinically altering liver function or Child-Pugh class.

Value of three-dimensional spiral CT hepatic angiography.

The aim of this study was to compare with conventional angiography images the diagnostic utility of three-dimensional CT hepatic angiography (CTHA) images reconstructed from spiral CT images obtained during direct injection of contrast material into hepatic arteries. Three-dimensional CTHA images were reconstructed from spiral CTHA images obtained during direct hepatic arterial contrast material injection in 22 patients. We used maximum-intensity-projection (MIP) and shaded-surface-display (SSD) techniques. We compared matched pairs of MIP CTHA images and SSD CTHA images with conventional angiograms for depiction of peripheral (segmental to subsegmental order branches) and proximal (common to proper) hepatic arteries as well as for conspicuity of the entire hepatic arterial tree in 22 patients and for conspicuity of tumors, recognition of tumor sites, and depiction of tumor-feeding arteries in 21 patients with malignant liver tumors. Our evaluations were performed in a blinded fashion by two experienced radiologists, who reached a consensus. (These radiologists also counted the number of tumors depicted by each method in the 21 patients with malignant liver tumors.) Depiction of peripheral and proximal hepatic arteries and conspicuity of the entire hepatic arterial tree were significantly better on conventional angiograms than on MIP CTHA images and SSD CTHA images. Conspicuity of tumors and recognition of tumor sites were significantly better on MIP CTHA images and SSD CTHA images than on conventional angiograms. Depiction of tumor-feeding arteries was significantly better on MIP CTHA images than on SSD CTHA images and conventional angiograms. For 47 malignant liver tumors, MIP CTHA images showed 40 (85%), SSD CTHA images showed 34 (72%), and conventional angiograms showed 20 (43%). MIP CTHA images showed liver tumors, tumor sites, and tumor-feeding arteries better than conventional angiograms. MIP was the preferred method for three-dimensional CTHA analysis.

Hepatic pseudolesion in the left lobe around the falciform ligament at helical CT.

To determine the prevalence and possible cause of pseudolesions in the left hepatic lobe around the falciform ligament at hepatic helical computed tomography (CT). Portal venous-dominant CT scans of 472 consecutive patients were reviewed. CT of the left hepatic lobe was performed after injection of contrast material into the portal vein in 73 patients, the hepatic artery in 32, and the internal thoracic artery in four. The scans were compared with those obtained at helical CT, and the findings were analyzed. Pseudolesions were seen on 64 (14%) of 472 helical CT scans and correlated well (accuracy, 96%) with portal perfusion defects. They were not more enhanced than the surrounding liver parenchyma at CT arteriography with hepatic artery injection but were enhanced in two patients at CT arteriography with internal thoracic artery injection. Pseudolesions are caused by portal perfusion defects and may receive an aberrant blood supply.

Preparation and biodistribution of yttrium-90 Lipiodol in rats following hepatic arterial injection.

In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate 90Y from strontium-90. 90Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while 90Sr was washed out. A hexadentate nitrogen-donor chelating ligand N,N,N',N'-tetrakis(2-benzymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained 90Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi 90Y-Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Kupffer Cells in Iodized Oil Embolization

Iodized oil is a common oily embolic agent used in chemoembolization for treating hepatic tumors. However, how the iodized oil is cleared from the liver has been an unsettled and controversial issue. In this study, the authors attempt to clarify whether Kupffer cells are involved in the clearance of iodized oil and to evaluate the effect of hepatic arterial injection of iodized oil on the functional status of Kupffer cells. Iodized oil was injected into the proper hepatic artery in 42 Fischer 344 rats. In vivo microscopy was performed immediately after and 1, 3, 7, 15, 30, and 60 days after injection. Electron microscopy was performed after in vivo microscopy. Kupffer cells actively captured and phagocytosed iodized oil droplets in the hepatic circulation. The number and functional status of Kupffer cells in the liver were significantly increased after the injection of the iodized oil and returned to normal when the liver was cleared of the oil. Kupffer cells play an important role in clearing iodized oil from the liver. Iodized oil activates the immune defense system in the liver, which may have a synergistic effect in tumor treatment.

Selective intraarterial methylene blue for pancreatic and duodenal endocrine tumors

Pancreatic and duodenal endocrine tumors can be difficult to localize intraoperatively. Three patients are described in whom selective intraarterial injection of methylene blue was used to correctly identify the position of an endocrine tumor. These patients had a duodenal gastrinoma, a pancreatic polypeptide-producing pancreatic islet cell tumor, and a duodenal somatostatinoma, respectively. Selective arterial secretin injection with hepatic vein gastrin measurement and selective arterial calcium injection with hepatic vein pancreatic polypeptide measurement were used to preoperatively identify the feeding artery. The duodenal somatostatinoma was identified by endoscopy. A catheter placed in the feeding artery just prior to surgery was used for injection of the methylene blue. The combination of selective arterial stimulation and selective arterial methylene blue injection is a promising method for helping surgeons localize elusive endocrine tumors in the duodenum and pancreas.

Role of the Hepatic Artery in the Metabolism of Phenacetin and Acetaminophen: An Intravital Microscopic and Multiple–Indicator Dilution Study in Perfused Rat Liver

We studied the pattern of intermixing of the hepatic arterial and portal venous flows in a perfused rat liver preparation under constant flow (12 ml/min) with intravital epifluorescent microscopy; changes in the steady state extraction ratio of carbon 14-labeled phenacetin and tritiated acetaminophen, probes metabolized primarily in perivenous and periportal regions of the rat liver, respectively; and the spaces accessed by noneliminated reference indicators introduced as a bolus into the hepatic artery and portal vein at different hepatic arterial/portal venous flow regimens of 0:12, 2:10 and 4:8. The sinusoidal velocities for the hepatic arterial- and portal venous (hepatic arterial/portal venous flow at 4:8)-infused fluorescein isothiocyanate-erythrocytes (100 microliters/min) were 327 +/- 78 and 301 +/- 63 microns/sec, respectively, and the velocity for the solely portal venous-perfused liver (12 ml/min) was 347 +/- 74 microns/sec; the flow-weighted sinusoidal velocity was highly correlated to the sinusoidal volume for the dually perfused rat liver. Small but significant decreases in the extraction ratio of [14C]phenacetin (from 0.989 to 0.984 and 0.980) and tritiated acetaminophen (from 0.631 to 0.607 to 0.563), delivered simultaneously into the hepatic artery and portal vein, were observed with an increment of hepatic arterial flow within the same liver preparation; oxygen consumption rate also fell slightly, in parallel fashion. When a multiple-indicator dilution dose containing chromium 51-labeled RBCs, iodine 125-labeled albumin and tritiated water or [14C]urea was injected into the hepatic artery (which accesses both the peribiliary capillary plexus [nonsinusoidal] and the sinusoidal bed) and portal vein (which enters only the sinusoids) at 10-min intervals within each steady state, the blood volume, total albumin space, albumin Disse space, total water and parenchymal cellular water spaces were unchanged after portal venous injection for all hepatic arterial/portal venous flow ratios, suggesting that the arterial flow is ineffective in perturbing average sinusoidal flow dynamics. However, slightly larger total water spaces were obtained with hepatic arterial injection. This excess water space was almost completely accounted for by the "nonsinusoidal" extravascular space associated with the peribiliary capillary plexus; it averaged 0.03 ml/gm and was independent of flow. The anomaly, a reduced flow-weighted sinusoidal velocity for the dually perfused liver, an unchanged diameter of the terminal hepatic venule (32 microns) among the hepatic arterial/portal venous flow ratios and the reduction in the extraction ratio of the drug probes and oxygen consumption rates suggest that some of the arterial flow must have entered the sinusoids somewhat downstream.

Hepatic artery and portal vein vascularization of normal and cirrhotic rat liver†

The hepatic artery and portal vein vascularization of seven normal and seven cirrhotic rats was evaluated by means of the multiple-indicator dilution technique using the flow-limited model analysis. Injected 15-micron microspheres were all trapped by the liver in normal and cirrhotic rats after portal vein and hepatic artery injections, ruling out the presence of intrahepatic shunts larger than 15 microns. The albumin curve was linearly displaced relative to the red blood cell curve in both groups of rats, indicating that albumin distribution remained compatible with the flow-limited distribution model. Albumin extravascular space was similar when measured following both routes of injection. Sucrose outflow profile was also compatible with the flow-limited model after portal vein injection in normal rats, but not in severely cirrhotic rats. In contrast, after hepatic artery injection in both normal and cirrhotic rats the sucrose curve was not linearly displaced compared with that of red blood cells; its curve peak was less delayed than its downslope. This finding indicates that, after hepatic artery injection, sucrose distribution was not compatible with the flow-limited model; moreover, its extravascular space was much larger than that after portal vein injection, particularly in cirrhotic rats. This phenomenon is best explained by the peribiliary capillary plexus, lying between terminal arteries and sinusoids, a plexus enlarged in cirrhotic livers. Finally, sinusoidal volume was apparently much larger after hepatic arterial injection compared with that after portal venous injection. This occurrence may well result from an unshared arterial sinusoidal bed or the peribiliary capillary plexus.

Determinants of long-term survival following hepatectomy for hepatocellular carcinoma, with special reference to patients surviving more than 10 years

To elucidate the determinants of survival and the clinicopathologic features of long-term survivors of resections for HCC, we reviewed 539 patients who had had hepatectomy alone or hepatectomy together with hepatic arterial ligation or ethanol injection for the treatment of hepatocellular carcinoma (HCC) at our department between 1973 and December 1992. Of these patients, 30% (79/264) survived for more than 5 years and 11% (10/87) for more than 10 years. All the long-term survivors had received curative resections. The 5- and 10-year survivors accounted for 58% (79/136) and 29% (10/35) of those with curative resections, respectively. Crucial determinants for long-term survival were the absence of portal invasion and satellite nodules, a diploid pattern of DNA content, and a curative resection. A curative resection for diploid HCCs led to much better survival rates (73%) at 5 years than such a resection for aneuploid HCCs (35%), and than for non-curative resections for aneuploid HCCs (0%). The history and tumor background of the ten patients who survived for more than 10 years were characterized by good reserve liver function, warranting a wider resection, predominance of female sex, single nodular growth, and the absence of poorly differentiated cells, in addition to the favorable conditions described above. Three of the ten patients developed a new lesion; these were successfully treated by re-resection or repeated arterial embolization, since they were confined to the remnant liver and showed single nodular growth without extranodular spread. This analysis indicates that hepatectomy is the option of first choice for HCC patients with the potential for cure and good reserve liver function.

Selective radionuclide localisation in primary liver tumours (pilot study).

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellullar carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I-Lipiodol can deliver highly selective internal irradiation to foci of HCC with evidence of objective response and may be the treatment of choice for patients with cirrhosis and a small tumour.

Hepatic Arterial Chemoembolization for Metastatic Endocrine Tumors

In patients with hepatic metastases from endocrine tumors, the safety and effectiveness of chemoembolization with ethiodized oil was determined and compared with those of embolization with particulate matter alone. Twenty patients with hepatic islet cell or carcinoid tumor metastases were treated with selective hepatic artery injection of doxorubicin and iopamidol emulsified in ethiodized oil, followed by gelatin foam powder embolization. In 16 patients with hormonally active tumors, hormone secretion decreased 90% (range, 69%-98%) in 10 days, with relief of symptoms in all patients. Average tumor size decrease was 84%; average hospitalization was 8 days. Seventeen patients are alive 6-27 months after embolization, and all are asymptomatic. Three patients died within 1 year after embolization of progressive disease outside the liver. Chemoembolization with doxorubicin emulsified in ethiodized oil and iopamidol is effective in the treatment of hepatic metastases from endocrine tumors. This technique appears to result in less morbidity than particulate embolization alone.

Usefulness of hepatic artery injection of iodized oil and 131I-labeled iodized oil before the therapeutic decision in hepatocellular carcinoma.

This study assesses the usefulness of intra-arterial injection of iodized oil (Lipiodol) as a tool for evaluating the therapeutic choice in a series of 72 consecutive patients with hepatocellular carcinoma (HCC). In 52 of these patients a scintigraphic study of the biodistribution of iodized oil was done, using 131I-iodized oil injection. A single tumor was detected in only 17 cases; 18 patients had a tumor involving only 1 lobe; in 7 cases CT scan disclosed a minute nodule in the opposite lobe of the main tumor. Eighteen patients had a portal thrombosis; in 12 of these cases CT scan showed iodized oil in the tumor emboli. The degree of intratumoral retention of iodized oil depended on the size of tumors and on the presence of arterioportal shunts. Our study demonstrates that only a few patients (4%) with HCC might benefit from curative surgery. The therapeutic benefit of methods using iodized oil injection might be estimated by means of its biodistribution variables (CT and/or scintigraphic data).

Dual contrast enhancement of both T1- and T2-weighted sequences using ultrasmall superparamagnetic iron oxide

BMS 180549 (previously AMI-227), an ultrasmall superparamagnetic iron particulate agnet, was investigated to determine its utility as a contrast agent on T 1-weighted, as well as T 2-weighted sequences, as a function of route of administration, (intravenous versus selective arterial) and concentration. Twelve farm pigs were divided into three groups of four each by route of administration (intravenous, selective superior mesenteric, or selective hepatic arterial injection). 10 μmol/kg and 20 μmol/kg dosages were given and evaluated both immediately after and 20–24 hr after contrast infusion, using both spin-echo and gradient-echo T 1 and T 2-weighted sequences. Significant postcontrast liver and spleen enhancement was noted at both concentrations, regardless of route of administration on both T 1- and T 2-weighted sequences. The earliest postcontrast T 1-weighted sequence obtained during the 1–3 min interval following IV administration of high dose (20 μmol/kg) contrast demonstrated an average of +42.8% liver and +249.0% spleen enhancement; 24 hr later this decreased to 0 and 7.2%, respectively. The earliest postcontrast T 2-weighted sequence obtained during the 8–17 min interval post high-dose IV contrast showed an average of −75.8% decrease in liver and −28.7% decrease in spleen signal intensity; 24 hr later the magnitude of these changes diminished to −33.1% and +2.5%, respectively. No significant difference was noted in liver or spleen enhancement, regardless of route of contrast administration (intravenous versus intraarterial).