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Background: A new multiphasic fast imaging technique, known as volume helical shuttle technique, is a breakthrough for liver imaging that offers new clinical opportunities in dynamic blood flow studies. This technique enables virtually real-time hemodynamics assessment by shuttling the patient cradle back and forth during serial scanning., Purpose: To determine optimal scan timing of hepatic arterial-phase imaging for detecting hypervascular hepatocellular carcinoma (HCC) with maximum tumor-to-liver contrast by volume helical shuttle technique., Material and Methods: One hundred and one hypervascular HCCs in 50 patients were prospectively studied by 64-channel multidetector-row computed tomography (MDCT) with multiphasic fast imaging technique. Contrast medium containing 600 mg iodine per kg body weight was intravenously injected for 30 s. Six seconds after the contrast arrival in the abdominal aorta detected with bolus tracking, serial 12-phase imaging of the whole liver was performed during 24-s breath-holding with multiphasic fast imaging technique during arterial phase. By placing regions of interest in the abdominal aorta, portal vein, liver parenchyma, and hypervascular HCCs on the multiphase images, time-density curves of anatomical regions and HCCs were composed. Timing of maximum tumor-to-liver contrast after the contrast arrival in the abdominal aorta was determined., Results: For the detection of hypervascular HCC at arterial phase, mean time and value of maximum tumor-to-liver contrast after the contrast arrival were 21 s and 38.0 HU, respectively., Conclusion: Optimal delay time for the hepatic arterial-phase imaging maximizing the contrast enhancement of hypervascular HCCs was 21 s after arrival of contrast medium in the abdominal aorta.

Purpose: To evaluate differences in the viscosity of a platinum iodized-oil suspension on the kind of platinum agent and temperature., Materials and Methods: Viscosities of a 70 mg miriplatin and 3.5 ml iodized-oil suspension (MO suspension) and that of 100 mg cisplatin and 10 ml iodized-oil suspension (CO suspension) were evaluated at three temperatures: 25, 37, and 50 °C. Iodized-oil was used as the control. Each liquid was injected into a capillary tube and allowed to drip separately. The liquid transit time was measured, and the viscosity of each liquid was calculated at each temperature., Results: The viscosity of each liquid decreased as the temperature increased: 43.3 ± 0.5, 39.2 ± 0.7, and 34.7 ± 0.6 mPa s for MO suspension, 41.3 ± 0.2, 36.9 ± 0.3, and 32.7 ± 0.9 mPa s for CO suspension, and 40.5 ± 0.2, 36.8 ± 0.2, and 33.8 ± 0.7 mPa s for iodized-oil at 25, 37, and 50 °C, respectively. The MO suspension group viscosity was significantly higher than that of the CO suspension group (p < 0.05) and the control (p < 0.05). Significant differences were found in viscosities among groups divided by temperature (25 °C-group vs. 37 °C-group, p < 0.05; 37 °C-group vs. 50 °C-group, p < 0.05)., Conclusion: The viscosity of the platinum iodized-oil suspension can be adjusted by changing temperature.

This study presents new important aspects in the design of contrast agents for X-ray preclinical imaging. The first one is a new simple formulation of long circulating contrast agents, formulated from a commercial iodinated oil, and resulting in CT contrast agents containing more than twice the iodine concentration commercial contrast agents. The second point is a methodological aspect, utilizing tangential filtration for reducing the residual surfactants in the bulk phase and serving as well for concentrating droplets (and iodine) in the suspension. The last point is a more general aspect regarding the influence of the free surfactant on the pharmacokinetics and biodistribution of the nano-emulsion droplets on mice. We showed that cross-flow filtration is efficient for concentrating the droplets and reducing the concentration of free surfactant from 10wt.% to 1wt.%, without any changes in the nano-emulsion droplet morphologies or surface properties. We also showed that the presence of free surfactant has a significant impact on the elimination way of the nano-emulsion droplets, shared between liver and kidneys. The purified nano-emulsions are preferentially eliminated by the kidneys in contrast to raw nano-emulsions, predominantly eliminated by the liver. In practice, for two similar suspensions, half-life decreases from 4.1±1.10h to 2.5±0.77h before and after purification. Since the design and development of long circulating systems are critical in numerous domains, and not for preclinical CT imaging, this study presents important results in that field, taken under a formulation and technical point of view., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The aim of the study was to compare iodine utilization from different sources by sows and their progeny and the levels of T3 and T4 in their serum., Design: Pregnant Czech Large White × Landrace sows were fed with an experimental KPK diet (a diet for lactating sows) 14 days before parturition until weaning (at a piglet age of 28 days). In group A (n=50, 10 sows, 40 piglets) the feed was supplemented with KI (0.6 mg of iodine per kg of feed). Iodine enriched alga Chlorella spp. (0.6 mg of iodine per kg of feed) was used as a supplement in group B (n=50, 10 sows, 40 piglets). In group C (n=50, 10 sows, 40 piglets) the sows were injected i.m. with IFAE at a dose of 100 mg of iodine per sow. Iodine, T3 and T4 were measured in each group for comparison of iodine utilization., Results: The use of IFAE resulted in higher serum concentrations in sows compared to KI and alga. In contrast, iodine concentrations in milk and piglets were lower when IFAE were used. We found a wide variation in the concentrations of T3 and T4 in the serum of piglets in all groups., Conclusion: Our results indicate a good utilization of iodized oil by sows. However, its transfer into milk is lower compared to the other iodine sources.

Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer with high morbidity. (131)I-lipiodol is used clinically and has been found to be effective for the treatment of HCC. However, this preparation has its limitations, including compromised yield and stability of exchange labeling and unnecessary dose burden from gamma emissions. In the present study, (177)Lu-oxine in lipiodol was considered as a possible alternative for radioiodinated lipiodol. Oxine or 8-hydroxyquinoline was labeled with (177)Lu obtained by neutron irradiation of natural lutetium. Under optimized conditions, the radiolabeled complex was obtained with yields >98% and adequate in vitro stability. (177)Lu-oxine dispersed in lipiodol showed appreciable uptake into rat liver cells (normal and HCC-induced) in vitro. (177)Lu-oxine-lipiodol showed initial localization in the liver, but subsequent leakage of radioactivity with deposition in the skeletal tissue was seen. The studies suggest that (177)Lu-oxine dispersed in lipiodol might not be suitable for treatment of HCC.

Purpose: The purpose of this study was to evaluate the pattern and the chronological change of iodized oil retention in a radiofrequency ablation (RFA)-induced vascular injury area as compared with that in recurrent hepatocellular carcinoma (HCC)., Materials and Methods: Informed consents from all the patients and approval from the institutional review board were obtained. The computed tomographic scans of 226 patients who underwent both RFA and subsequent transcatheter arterial chemoembolization for recurrence were retrospectively reviewed. The RFA-induced vascular injury area that did not have HCC recurrence in it were examined and assessed whether iodized oil was retained after transcatheter arterial chemoembolization. We evaluated the incidence, the shape, and the duration of the iodized oil retention in the RFA-induced vascular injury area and compared them with those found in recurrent HCC from the same patient. The rate of misinterpretation was calculated., Results: Of 59 RFA-induced vascular injury areas that were within the range of segmental embolization, 33 RFA-induced vascular injury areas (55.9%) in 31 patients retained iodized oil. The shapes of the iodized oil in the RFA-induced vascular injury area were diffuse-dense (n = 13), diffuse-faint (n = 8), nodular-dense (n = 8), or nodular-faint (n = 4). In 29 (93.5%) of 31 patients, at least one recurrent HCC retained iodized oil, and they were all nodular-dense in shape. The duration of the retention in RFA-induced vascular injury area (mean [SD], 3.3 [3.2] months) was significantly shorter than that in recurrent tumors (21.2 [12.5] months, P < 0.001). In 21.2% (7/33) of the cases, the iodized oil density in the RFA-induced vascular injury area was clinically misinterpreted as recurrent HCC., Conclusions: The RFA-induced vascular injury area frequently retains iodized oil, which could mimic recurrent HCC. However, we determined that iodized oil in the RFA-induced vascular injury area differs from that in HCC in variety in shape and shorter duration of retention.

Background: Cisplatin is one of the most effective chemotherapeutic agents against a variety of human cancers. Its usefulness is limited by its toxicity to normal tissues, including cells of kidney proximal tubules., Purpose: To evaluate the effect of sodium thiosulfate (STS) on cisplatin clearance after transcatheter embolization (TAE) with a lipiodol-platinum suspension (LPS) in patients with hepatocellular carcinoma (HCC)., Material and Methods: The study was performed prospectively in a randomized manner. HCC patients underwent intra-arterial LPS embolization with (n=17) and without (n=15) an intravenous STS infusion. Renal toxicity was estimated and free and total platinum concentrations were assessed for 7 days after treatment., Results: After treatment without STS, there was a mild elevation of serum creatinine and a decrease in creatinine clearance. With STS, there was no significant difference before and after treatment in mean serum creatinine and creatinine clearance; free platinum disappeared completely within 120 min. In patients treated without STS, free platinum decreased rapidly within 120 min; this was followed by a gradual decrease during the next 7 days., Conclusion: STS seems effective against the renal toxicity of cisplatin. However, in the presence of STS, the anticancer effect of cisplatin may be decreased due to the accelerated disappearance of platinum.

A new phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol) was developed as a boron carrier for the boron neutron capture therapy (BNCT) of hepatoma in Taiwan. The biodistribution of both PBAD-lipiodol and BPA-fructose was assayed in GP7TB hepatoma-bearing rat model. The highest uptake of PBAD-lipiodol was found at 2h post injection. The application of BNCT for the hepatoma treatment in tumor-bearing rats is suggested to be 2-4h post PBAD-lipiodol injection., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Abstract Transarterial embolization by the intra-arterial administration of 131I-lipiodol is a modality used in the treatment of liver cancer. Long-chain fatty acids, being highly lipophilic, are also known to localize in the liver, thus constituting favorable vectors for this modality of treatment. Toward this, we envisaged the derivatization of 15-bromopentadecanoic acid, rendering it suitable for incorporation of a tridentate chelating moiety, for radiolabeling with the [99mTc(CO)3(H2O)3]+ precursor. The complex prepared, being lipophilic, was expected to behave as a lipiodol surrogate. The radiolabeled complex could be obtained in >95% radiochemical yield, as characterized by high-performance liquid chromatography. The intravenous injection of the radiolabeled complex in mice resulted in 23.5% +/- 4.3% uptake of injected dose (ID) organ in the liver at 3 hours postinjection. However, the uptake of the lipiodol suspension of the complex at 3 hours postinjection in the liver was found to be 43.8 +/- 13.4% ID/organ, when injected via the portal vein.

Objective: Intra-arterial administration of beta-emitting radionuclides in the form of suitable radiopharmaceuticals is one of the promising modalities for the treatment of liver cancer. Ho [T1/2=26.9 h, Ebeta(max)=1.85 MeV, Egamma=81 keV (6.4%)] could be envisaged as an attractive radionuclide for the use in liver cancer therapy owing to its high-energy beta-emission, short half-life and feasibility of its production with adequately high specific activity and radionuclidic purity using moderate flux reactors. Lipiodol is chosen as the vehicle to deliver localized doses of ionizing radiation to liver cancer cells after intra-arterial hepatic infusion as it is selectively retained in the vascular periphery of the proliferating cells., Methods: Ho was produced by thermal neutron bombardment on a natural Ho2O3 target at a flux of approximately 6 x 10 n/cm.s for 7 days. Radiolabelled lipiodol was prepared by dispersing the Ho-oxine complex in lipiodol. The biological behaviour of Ho-oxine-lipiodol was studied by biodistribution and imaging studies in normal Wistar rats., Results: Ho was produced with a specific activity of 9.25-11.10 TBq/g and radionuclidic purity of approximately 100%. The Ho-labelled oxine complex was prepared in high yield (approximately 97%). Approximately, 95% of the Ho activity was dispersed in lipiodol within 30 min. The resulting radiolabelled preparation was found to exhibit good stability in physiological saline and human serum up to 3 days. The biodistribution and imaging studies revealed satisfactory hepatic retention (88.43+/-2.85% of injected activity after 2 days) with insignificant uptake in any other major organ/tissue except skeleton (6.44+/-1.07% at 2 days postinjection)., Conclusion: The Ho-oxine-lipiodol preparation exhibited promising features in preliminary studies and warrants further investigation.

There is limited information about the retention of lipiodol in the parotid gland after parotid gland sialography. This study assesses the prevalence of lipiodol retention after parotid sialography and determines if retention of lipiodol is related to the sialography technique or the underlying salivary gland pathology. Using the electronic hospital database (1996-2006), 66 out of 565 patients were identified who had additional maxillofacial radiographic examinations after the initial sialography. Additional radiographs up to October 2007 were included; these were orthopantomographic radiographs in all cases. In 28 patients (42%) signs of lipiodol retention were observed (mean radiographic follow-up: 15+/-13 months). Retention was characterized by small radiopaque spots in the periphery of the gland. Lipiodol retention was predominantly associated with a fausse route (n=8) or the presence of salivary gland disease (sialectasia; n=17). In 9 patients with signs of lipiodol retention, a series of radiographs was available. Lipiodol radiodensities decreased in size during 28 months, and could disappear gradually (follow-up 14-57 months). Despite the high frequency of retention of small depots of lipiodol for years after sialography in patients subjected to additional radiographic examinations, no clinically adverse effects were observed.

A lipiodol solution of (188)Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol ((188)Re-HDD/lipiodol) is in clinical study for liver cancer therapy. However, formulation of it is difficult due to highly active and unstable sulfhydryl groups. We produced new kits using diacetylated HDD (AHDD), in which sulfhydryl groups are protected. We found that AHDD kit can replace HDD kit due to an increased stability for formulation, the better radiolabeling efficiency (78%) and the equivalent biodistribution pattern in mice.

Purpose: ZT glue immobilizes iodinated oil to raise treatment efficiency., Materials and Methods: ZT glue and iodinated oil were mixed at a series of volume ratios on a level surface which be put vertically after 30 min. Five Sprague-Dawley rats (group 1) were subcutaneously injected in the groin with ZT glue and (131)I-iodinated oil (volume ratio at 1:4, 0.1 ml per rat, (131)I activity 13.6 x 37 x 10(3)Bq), at 1, 8, 12, and 27 days, a SPECT plain scan was performed to observe the (131)I distribution in the body, and to calculate the gamma counts at the site of injection. At 28 days, the rats were sacrificed and organs were collected. Iodinated oil states at the injection spot were recorded. Specimens from organs and the injection spot were used to detect gamma counts. Another five Sprague-Dawley rats (group 2) were subcutaneously injected (131)I-iodinated oil in the groin as control group. Through portal vein, five rabbits right liver lobe received (131)I-iodinated oil (1 ml, 20 x 37 x 10(3)Bq)+ZT glue (0.25 ml). gamma counts in the liver region were recorded on days 0, 1, 2, 3, 4, 5, 6, 7, 9, 12, 15, 21, 27, and 33 after surgery. Then, gamma counting and pathological examination of the liver specimen and the lung specimen were performed. All gamma counts data was processed by INDFIT1.0 software that was designed in our laboratory to establish nuclide metabolic equation., Result: The mixed iodinated oil above the volume ratio of 1:12 stop at level surface local. At rat the injection site, the nuclide stagnation time of group 1 are longer than those of group 2, and the biological half-life of group 1 is four times that of group 2. Single agent analysis of variance comparing the biological half-life: F value is 81.999, p<0.001. No visible damage was seen in the rat organs. All rat organs except the liver had no statistically significant gamma counts difference. Tissue gamma counts at the site of injection at day 28 had statistically difference between the two rat groups, F value is 5.608, p=0.045. The iodinated oil metabolic patterns in rabbit liver revealed two portions, the rapid and the slow. ZT glue rabbit group had higher slow proportion than iodinated oil group. Pearson Goodness-of-Fit Chi-square test found the Chi-square value was 25.433, d.f.=6, p<0.0001. ZT glue rabbit group right liver lobe has iodinated oil and ZT glue depositing, some liver cells were degenerated and vacuolated in the cellular plasma. Fibrous tissue proliferated around hepatic portal canal regions., Conclusion: ZT glue fixed iodinated oil is possible in vivo. This provides a new potentiality to delay iodinated oil metabolic in clinical liver cancer interventional treatment.

Purpose: The intra-arterial administration of lipiodol-ethanol mixture (LEM, mixed in 4:1 by volume) through the hepatic artery is known to produce dual hepatic-arterial and portal-venous embolization that could be a potent treatment of hepatocellular carcinoma. The aim of this animal experiment was to study the effectiveness and safety of such transarterial ethanol ablation in cirrhotic livers., Methods: The study model consisted of a control group of 6 normal rats and a study group of 6 cirrhotic rats. LEM was infused intra-arterially into the right lobe of all 12 rats after selective catheterization under microscopic observation. LEM distribution within the hepatic vasculature, liver function tests, change in liver volume, and histology of the embolized lobe were studied., Results: The radiographs showed peripheral distribution of LEM within the portal venule in the right lobe of all rats. There was a marked reduction in the volume of right lobe 14 days after LEM, with an average reduction of 63.4 +/- 16.9% and 59.4 +/- 20.6% observed in the control group and study group, respectively. The difference between the 2 groups was not statistically significant. Before LEM treatment, there was a difference between the 2 groups (P = 0.002) regarding the plasma level of albumin and bilirubin, indicating that the blood test was sensitive enough to differentiate the liver function status between the normal rats and cirrhotic rats. On day 14, there was no difference between the 2 groups in plasma albumin, bilirubin, and ALT levels (P = 0.065, 0.818, 0.589), indicating almost equal extent of hepatic reaction towards LEM administration in normal and cirrhotic rats. On day 14, histologic study showed complete vascular infarction in 90% to 100% of the right lobe in both groups., Conclusion: Intraarterial ethanol ablation with LEM is equally effective in causing infarction of hepatic tissue in both normal and cirrhotic liver; it can be tolerated with equal safety by both normal and cirrhotic rats in this animal experiment.

To evaluate the usefulness of combination chemotherapy with cisplatin powder, which was newly designed for intra-arterial infusion (IA CALL) and lipiodol, for the VX 2 liver cancer model of the rabbit, sequential change of the plasma platinum concentration within the first 24 hours, as well as the tissue platinum concentration at 24 hours was measured after intra-arterial infusion of IA CALL. The infused materials were either IA CALL alone (C) or the combination of lipiodol+IA CALL (CL). In addition,the reduction rate of the VX 2 tumor was calculated among four therapeutic groups (C, CL, lipiodol alone (L), and saline alone (S)) after one week of intra-arterial infusion on the basis of 7.0 Tesla MR images. Total plasma platinum concentrations within the first 24 hours were kept low in group CL. No increase in the tissue platinum concentration in group CL was observed. On the other hand, the tumor reduction rate tended to be higher in group CL (group CL>group L=group C>group S). These results suggested that the intra-arterial infusion of IA CALL with lipiodol is more effective than that of IA CALL alone.

Purpose: The aim of this study was to investigate the feasibility of administering increasing activities of (188)Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for the treatment of hepatocellular carcinoma (HCC) in patients with well-compensated cirrhosis., Methods: The activity levels were increased by 1.1 GBq/step after a 6-week interval without unacceptable adverse events in at least five consecutive patients. Absorbed doses to the various organs were calculated according to the MIRD formalism, based on three gamma-scintigraphic studies. Response was assessed by means of MRI and alpha-fetoprotein (AFP) monitoring., Results: Thirty-five treatments were carried out in 28 patients. Activities from 4.8 to 7.0 GBq (188)Re-HDD/lipiodol were administered via a transfemoral catheter. The mean absorbed dose to the liver (including tumour) was 7.6+/-2.2, 9.8+/-4.9 and 15.2+/-4.9 Gy for the 4.8-, 5.9- and 7.0-GBq groups, respectively. Treatment was well tolerated at all activity levels. Further escalation of the administered activity was not feasible owing to limitations related to the radiolabelling procedure. Response assessment on MRI showed partial response, stable disease and disease progression in 1, 28 and 2 assessable treatments, respectively. In 8 of 17 treatment sessions with an initially elevated AFP, a reduction ranging from 19% to 97% was observed 6 weeks later., Conclusion: Following the intra-arterial administration of 4.8-7.0 GBq (188)Re-HDD/lipiodol in patients with HCC and well-compensated liver cirrhosis, no severe adverse events occurred. Further escalation was not feasible owing to limitations in the radiolabelling procedure.

Aim: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model., Methods: 5'-Isothiocyanate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6) ultra-fluid lipiodol was administrated via hepatic artery. Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope., Results: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues., Conclusion: ASODN can transfect Walker-256 cells. ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.

Unlabelled: The aim of this study was to investigate the pharmacokinetics, organ dosimetry, and toxicity after the intraarterial administration of (188)Re-labeled 4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for palliative treatment of hepatocellular carcinoma (HCC). A secondary objective was to document the response., Methods: A mean activity of 3.60 GBq (188)Re-HDD/lipiodol (range, 1.86-4.14 GBq) was administered to 11 patients (16 treatment sessions) via a transfemoral catheter. The pharmacokinetic and dosimetric data were collected by means of venous blood samples, urine collections, and 4 or 5 gamma-scintigraphies over 76 h. Absorbed doses to the various organs were calculated according to the MIRD formalism, using the MIRDOSE3.1 software. The toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria scale. The response was evaluated on MRI and by monitoring of the tumor marker., Results: A fast blood clearance of the injected activity was observed with a calculated effective half-life of 7.6 +/- 2.2 h (+/-SD) in blood. The predominant elimination of the activity was through urinary excretion with a mean renal clearance of 44.1% +/- 11.7% (+/-SD) of the injected activity within the 76 h after administration. Fecal elimination was negligible. The calculated whole-body effective half-life was 14.3 +/- 0.9 h (+/-SD). The absorbed dose to the liver tissue, the lungs, the kidneys, and the thyroid was 4.5 +/- 1.9, 4.1 +/- 1.2, 0.9 +/- 0.7, and 0.3 +/- 0.1 Gy, respectively. Treatment was well tolerated, except in 2 patients. One Child B patient experienced a worsening of his liver dysfunction (hyperbilirubinemia) and another patient experienced dyspnea and coughing. Response assessment on MRI showed 1 case of partial response, disease stabilization in 11 treatments, and progressive disease in 1 treatment. In 5 of 8 treatment sessions with an initially elevated alpha-fetoprotein, a reduction (range, 19%-90%) was observed 6 wk later., Conclusion: After the intraarterial administration of 3.60 GBq (188)Re-HDD/lipiodol, a fast clearance of the activity appearing in the blood is observed and the predominant elimination is through urinary excretion. The tolerance as well as the preliminary response rates of the present phase I study are encouraging.

Objective: To study the phamacokinetics and targeting characteristics of adriamyin in dogs following embolization of hepatic artery with adriamyin-lipiodol emulsion (AD-E)., Methods: After injection of adriamycin solution and the emulsion, respectively, into the hepatic artery via a femoral artery of the dogs, the concentration of adriamycin in the peripheral venous blood and hepatic tissue were determined by high-performance liquid chromatography., Results: The concentration of adriamycin in peripheral venous blood was significantly lowered after AD-E embolization in comparison with that after adriamycin solution injection. Adriamycin concentration in the hepatic tissue at 10, 24, and 48 h after AD-E embolization was 5.42, 3.33 and 2.38 times that of adrimycin solution group, respectively., Conclusion: Compared to adriamycin solution, AD-E as an embolic agent can significantly alter the serum pharmacokinetics and liver targeting characteristics of adriamycin.

Background: Although intra-arterial radiation therapy with 131I-lipiodol is a useful therapeutic approach to the treatment of hepatocellular carcinoma, various disadvantages limit its use., Aim: To describe the development of a method for the labelling of lipiodol with 188Re-SSS (188Re (S2CPh)(S3CPh)2 complex) and to investigate its biodistribution after injection into the hepatic artery of rats with hepatoma., Methods: 188Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 188Re, in cold lipiodol. The radiochemical purity (RCP) of labelling was checked immediately. The 188Re-SSS lipiodol was injected into the hepatic artery of nine rats with a Novikoff hepatoma. They were sacrificed 1, 24 and 48 h after injection, and used for ex vivo counting., Results: Labelling of 188Re-SSS lipiodol was achieved with a yield of 97.3+/-2.1%. The immediate RCP was 94.1+/-1.7%. Ex vivo counting confirmed a predominantly hepatic uptake, with a good tumoral retention of 188Re-SSS lipiodol, a weak pulmonary uptake and a very faint digestive uptake. The 'tumour/non-tumoral liver' ratio was high at 1, 24 and 48 h after injection (2.9+/-1.5, 4.1+/-/4.1 and 4.1+/-0.7, respectively)., Conclusions: Using the method described here, 188Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. The biodistribution in rats with hepatoma indicates a good tumoral retention of 188Re-SSS lipiodol associated with a predominant hepatic uptake, a weak pulmonary uptake and a very faint digestive uptake. This product should be considered for intra-arterial radiation therapy in human hepatoma.

Purpose: To compare the prevalence of arterioportal (AP) shunting associated with (a) small (< or =3 cm) hemangiomas and (b) hepatocellular carcinomas (HCCs) (< or =3 cm) at two-phase helical computed tomography (CT)., Materials and Methods: Two-phase helical liver CT was performed in 107 patients (61 men, 46 women; age range, 25-73 years; mean, 48.6 years) with 169 small hemangiomas and in 384 patients (292 men, 92 women; age range, 18-82 years; mean, 58.3 years) with 598 HCCs 3 cm or smaller. Diagnosis of HCC was verified with histologic findings (n = 30) or typical imaging and clinical findings (n = 568); that of all hemangiomas was verified with typical imaging and clinical findings. Three radiologists retrospectively reviewed all CT images in consensus. Contrast material-enhanced CT scans were obtained during the hepatic arterial and portal venous phases. AP shunt was considered to be present when wedge-shaped or irregularly shaped homogeneous enhancement peripheral to tumor appeared at hepatic arterial phase CT and isoattenuation or slight hyperattenuation in that area appeared at portal phase CT. The prevalence of AP shunting associated with hemangiomas and that associated with HCCs were compared with multivariate model testing. Speed of lesion enhancement (rapid enhancement, when extent of intratumoral enhancement at hepatic arterial phase CT was >50%; slow enhancement, when extent of intratumoral enhancement was < or =50%) and presence of AP shunt were correlated with chi2 or Fisher exact testing., Results: AP shunts were more frequently found in hemangiomas (36 lesions [21.3%]) than in HCCs (25 lesions [4.2%]) (P <.001). Twenty-four (38%) of the 64 hemangiomas with rapid enhancement had AP shunts, whereas only 12 (11.4%) of the 105 hemangiomas with slow enhancement had AP shunts (P <.001). There was no significant difference between prevalence of AP shunt in the 573 HCCs with rapid enhancement (24 lesions, 4.2%) and that in the 25 HCCs with slow enhancement (one lesion, 4.0%)., Conclusion: AP shunts were more frequently seen at two-phase helical CT in small hepatic hemangiomas than in HCCs and thus represent a suggestive but not specific finding of hemangioma. Small hemangiomas with AP shunts tend to show rapid rather than slow enhancement., (Copyright RSNA, 2004)

Radiolabeled Lipiodol has routinely been used in hepatoma therapy. In this article an attempt to develop a new (188)Re-ECD/Lipiodol radiopharmaceutical, in which the chelating agent ECD (ethyl cyteinate dimer), is the constituent of the known brain perfusion agent (99m)Tc-ECD, and an evaluation of its stability and biodistribution in rats with hepatic tumors is presented. First, (188)Re-ECD was prepared in a vial, followed by extraction with Lipiodol to get the final product, (188)Re-ECD/Lipiodol. The optimal labeling conditions for (188)Re-ECD were: (1) tartaric acid which is better than EDTA as a weak chelating agent; and (2) 15 mg of SnCl(2), as the reducing agent, and 5-10 mg of tartaric acid in each vial had a better labeling yield. The radiochemical purity of (188)Re-ECD/Lipiodol was more than 94%. Twenty-four male Sprague-Dawley rats with liver tumors were sacrificed at 1, 24, and 48 h (eight rats each time) after an injection of approximately 7.4 MBq of (188)Re-ECD/Lipiodol via the hepatic artery. The radioactivity in the liver tumor is significantly high following therapeutic arterial injection, and relatively low in other organs including the bone, spleen, brain, thyroid, stomach, muscle, blood, and testis throughout this study. In conclusion, the new preparation of (188)Re-ECD/Lipiodol is a candidate agent for the treatment of liver cancer.

Purpose: Boron neutron capture therapy (BNCT) is particle radiotherapy with alpha ((4)He) particle and recoiled lithium nucleus ((7)Li) derived from a reaction of boron ((10)B) and thermal neutron. We investigated applying BNCT to malignant liver tumors. The purpose of the present study was to reveal the efficacy for administration of emulsion of a boron compound (sodium borocaptate; BSH) and lipiodol via a hepatic artery using a rat liver tumor model., Methods and Materials: Rat liver tumors were developed by direct injection of Walker 256 cells into the liver parenchyma. BSH (75 mg/kg)/lipiodol (0.3 mL/kg) emulsion was administered via the hepatic artery. Boron concentrations in the tumors, liver, and blood were measured at 1, 6, and 12 h after administration. Neutron capture radiography (NCR) was taken to confirm the selective accumulation of (10)B in the liver tumors., Results: Boron concentrations in the liver tumors and the tumor/liver (T/L) boron concentration ratio at 1, 6, and 12 h after administration of BSH/lipiodol emulsion (concentration: T/L ratio) were 479.2 ppm: 4.0, 197.3 ppm: 14.9, and 96.5 ppm: 6.6, respectively. Highly selective irradiation was clearly demonstrated by the NCR images., Conclusions: Intra-arterial administration of BSH/lipiodol emulsion is effective method for delivering high concentration of (10)B selectively to the liver tumors.

Unlabelled: One approach to treatment of primary hepatocellular carcinoma (HCC) is intraarterial injection of (131)I-lipiodol. Although clinical results have been positive, the therapy can be improved by using (188)Re instead of (131)I as the radionuclide. (188)Re is a high-energy beta-emitter, has a shorter half-life than (131)I, and has only low-intensity gamma-rays in its decay. The present study compared the cytotoxic effect of the radionuclide therapy in HCC patients treated with (131)I-lipiodol and (188)Re-4-hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)/lipiodol. To this end, dicentric chromosomes (DCs) were scored in metaphase spreads of peripheral blood cultures. The equivalent total-body dose was deduced from the DC yields using an in vitro dose-response curve., Methods: Twenty (131)I-lipiodol treatments and 11 (188)Re-HDD/lipiodol treatments were performed on, respectively, 16 and 7 patients with inoperable HCC. Patients received a mean activity of 1.89 GBq of (131)I-lipiodol or 3.56 GBq of (188)Re-HDD/lipiodol into the liver artery by catheterization. For each patient, a blood sample was taken during the week before therapy. A blood sample was also taken 7 and 14 d after administration for the patients treated with (131)I-lipiodol and 1 or 2 d after administration for the patients treated with (188)Re-HDD/lipiodol., Results: The mean DC yield of (188)Re-HDD/lipiodol therapy (0.087 DCs per cell) was significantly lower than that of (131)I-lipiodol therapy (0.144 DCs per cell) for the administered activities. Corresponding equivalent total-body doses were 1.04 Gy for (188)Re-HDD/lipiodol and 1.46 Gy for (131)I-lipiodol. Data analysis showed that, in comparison with (131)I-lipidol, (188)Re-HDD/lipiodol yielded a smaller cytotoxic effect and a lower radiation exposure for an expected higher tumor-killing effect., Conclusion: (188)Re is a valuable alternative for (131)I in the treatment of HCC with radiolabeled lipiodol, and a dose escalation study for (188)Re-HDD/lipiodol therapy is warranted.

Although intra-arterial radiotherapy with (131)I-labelled lipiodol is a useful therapeutic approach in the treatment of hepatocellular carcinomas, various disadvantages limit its use. Here we describe the development of (188)Re-SSS lipiodol, as well as its biodistribution in the healthy pig after injection into the hepatic artery. The (188)Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with (188)Re, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 and 48 h. The (188)Re-SSS lipiodol was injected into the hepatic artery of six healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo counting. An autoradiographic study was performed in three cases. (188)Re-SSS lipiodol was obtained with a yield of 87%+/-9.1%. The immediate RCP was 93%+/-3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%+/-1.5% of the activity remained in the lipiodol with an RCP of 91%+/-4%. Ex vivo counting confirmed the predominantly hepatic uptake and revealed weak lung and intestinal uptake. There was very weak urinary elimination (2.3%+/-0.5% at 48 h) and a slightly higher level of intestinal elimination (4.8%+/-1.9% at 48 h). The autoradiographic studies showed (188)Re-SSS lipiodol to be located mainly in sinusoids, like (131)I-lipiodol. By using the method described here, (188)Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. Its biodistribution in the healthy pig is in agreement with data published elsewhere concerning other types of radiolabelling used for lipiodol, except for the very weak urinary and intestinal elimination, which probably indicates better stability of (188)Re-SSS labelling.

Background: We develop a method for the radiolabelling of Lipiodol with Tc, using a lipophilic complex, [99mTc-(S2CPh)(S3Ph)2], dissolved in Lipiodol (99mTc-SSS Lipiodol)., Results: The labelling yield is high (96 +/- 0.8%), and the radiochemical purity satisfactory (92 +/- 2.6%). This labelling is reproducible and stable for up to 24 h in vitro. Studies carried out after injection into the hepatic artery of the healthy pig show that the biodistribution of 99mTc-SSS Lipiodol is comparable with that observed for 188Re Lipiodol., Materials and Methods: The 99mTc-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 99mTc, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 h. The 99mTc-SSS lipiodol was injected into the hepatic artery of four healthy pigs for an ex-vivo biodistribution study. An autoradiographic study was performed in two cases., Conclusions: Apart from the specific interest of a Lipiodol-bearing technetiated agent for carrying out dosimetric studies, the labelling of Lipiodol with 99mTc is a preliminary step towards the use of radiolabelling with the 188Re analogue.

Unlabelled: It has been reported that lipiodol solution of (188)Re-labeled 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N(2)S(2) derivative, shows excellent targeting of liver cancer after transhepatic arterial embolization (TAE). However, its tumor retention is not high enough to treat liver cancer. Therefore, a new form of TDD, 4-hexadecyl-TDD (HDD), was developed to improve tumor retention by introducing a long alkyl chain. In this study, we compared the tumor retention properties of (188)Re-HDD/lipiodol and (188)Re-TDD/lipiodol, using a rabbit liver cancer model, and performed dosimetry using the results., Methods: The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE was performed on 3 rabbits with (188)Re-TDD/lipiodol and on 4 rabbits with (188)Re-HDD/lipiodol, and conjugated anterior and posterior planar scans were obtained at 1, 2, 6, 24, and 48 h after TAE. From these images, tumor retention was calculated and compared between (188)Re-TDD and (188)Re-HDD. Afterward, the required dose of radioactivity and the radiation dosimetry for exposure of major organs were calculated using MIRDOSE3.1 software., Results: The residence times of radioactivity in the liver were 10.2 +/- 1.0 h in the (188)Re-TDD group and 17.6 +/- 0.8 h in the (188)Re-HDD group (P = 0.034). The required radioactivity for 100 Gy of irradiation to 2.64- to 5.27-cm tumors was 142-1,070 MBq of (188)Re-HDD in the rabbit model. The radiation exposures for the major organs were within the tolerable range, and the S-value for the whole body (effective dose equivalent) was calculated to be 0.209 mSv/MBq., Conclusion: Introduction of a long alkyl chain significantly improved the tumor retention of (188)Re-HDD/lipiodol, compared with that of (188)Re-TDD/lipiodol. Moreover, the required radioactivity for humans and the radiation exposure were within the feasible range for clinical application.

Patient dosimetry data for intra-arterial()iodine-131 lipiodol therapy for hepatocellular carcinoma (HCC) are scarce. The aim of this study was to determine the absorbed dose (D) to the tumour and healthy tissues, as well as the effective dose (E), by different methods for 17 therapies in 15 patients who received a mean activity of 1.9 GBq (SD 0.2) (131)I-lipiodol. Eight patients received thyroid blocking by potassium iodide (KI). Patient dosimetry was performed based on bi-planar total body scans using the Monte Carlo simulation program MCNP-4B and the MIRDOSE-3 standard software program. CT images of each patient were used to determine liver and tumour volume and position. The total body dose to the patient was also determined by biological dosimetry with the in vitro micronucleus (MN) assay. From the increase in micronucleus yield after therapy, the equivalent total body dose (ETBD) was calculated. Results for D and E were comparable between MCNP and MIRDOSE (liver: mean 7.8 Gy, SD 1.8, lungs: 6.8 Gy, SD 2.9, E: 2.01 Gy, SD 0.58). MIRDOSE gave a systematic overestimation for the tumour dose, especially for tumours <3 cm (15%). The MCNP method is more accurate since the dose contributions from tumour to organs and vice versa can be accounted for. The absorbed dose to the thyroid was significantly lower for patients who received KI (7.2 Gy, SD 2.2) than for the other patients (13.8 Gy, SD 5.0). MN yields could be obtained for only 12 of the 17 therapies due to hypersplenism. A mean ETBD of 1.66 Gy (SD 0.73) was obtained, but the MN results showed no correlation between the ETBD and the total body dose values of the physical dosimetry. Also, in all except one of the patients, no further reduction in the number of thrombocytes was observed after therapy, probably due to the existing hypersplenism. It is concluded that in view of the high E values, patient dosimetry is necessary for patients receiving (131)I-lipiodol therapy. Except in the case of the smaller tumours, comparable results were obtained with MCNP and MIRDOSE. Due to hypersplenism, biological dosimetry results based on the MN assay are not reliable.

Several authors have demonstrated the good tolerance of hepatic intra-arterial 131I-Lipiodol therapy and report survival rates of 21-25% after 1 year in inoperable patients. This study explored the possibility that more selective hepatic arterial instillation could be a strategy for increasing tumoural uptake and response of 131I-Lipiodol. Between June 1999 and September 2001 we selected 24 patients: 14 received a selective instillation of 131I-Lipiodol to the proper hepatic artery (SEL group); and 10 received a hyperselective instillation in the right or left hepatic artery (HYP-SEL group). The individual 131I-Lipiodol activity as a per cent of the injected activity per millilitre of tumour (%IA/ml tumour) was correlated with the selectivity of instillation in 28 tumours and with tumour response in 24 tumours. Differences in tumour response or tumour uptake between the SEL and HYP-SEL groups were not significant. In general, we observed a %IA/ml tumour of 0.05-2.6% for the uptake of 131I-Lipiodol. The uptake was significantly higher in responsive disease than in stable or progressive disease (P=0.002). A large tumour volume was invariably related to low uptake of 131I-Lipiodol and progressive disease (P=0.008). In conclusion, our study does not support the general use of hyper-selective or super-selective intra-arterial administration of 131I-Lipiodol. This result may be extrapolated to similar types of intra-arterial, loco-regional hepatic radionuclide therapy.

Objective: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to determine if such particles are cleared from the liver., Method: A lobe of normal liver in three pigs was arterially embolized with 300 mg of gamma-Fe2O3 particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated microspheres (32 microm) suspended in 1% tween-water. Samples of liver and blood were obtained before infusion, and at 60 min and 28 days after arterial infusion. At 28 days, samples of lung and other abdominal viscera were also obtained. The tissue samples were chemically analysed for iron content, and submitted to histopathological examination., Results: There was no significant reduction in the hepatic iron concentration in either treatment group 28 days after infusion. Both types of particles illicited an immunogenic response and were extensively phagocytosed in the liver. The particle/lipiodol suspension caused extensive necrosis of liver, while the microsphere/tween-water suspension was well tolerated. Small amounts of both types of ferromagnetic particles embolized in the lungs, but there was no evidence of embolization into other organs. There were no haematological or biochemical changes and all subjects experienced uneventful 28-day survivals., Conclusion: This study has shown that, although arterially infused ferromagnetic particles were extensively phagocytosed, there was no significant hepatic clearance 28 days after infusion. It also determined that the suspension of 150 nm ferromagnetic particles in lipiodol was too vaso-occlusive for use in hepatic tissue. However, the suspension of 32 microm microspheres containing ferromagnetic particles in tween-water was safe and well tolerated.

Background: In order to fight against iodine deficiency, the essential cause of endemic goiter and cretinism, several health organizations promoted campaigns of iodinated oil (Lipiodol UF) administration using iodinated oil administered intramuscularly. However, it seems preferable to administer iodinated oil orally, as this is more appropriate and since the efficacy of this route has been demonstrated as well as for intramuscular route by controlled clinical trials., Objective: To assess the bioavailability of iodinated oil (Lipiodol UF) administered via two different administration routes and the safety profile of this agent., Design: A randomized bioavailability study was performed comparing a single oral dose of 3 capsules (570 mg of iodine) vs a single intramuscular injection of 1 ml of Lipiodol UF (480 mg of iodine) in 36 healthy subjects followed for 9 months., Results: The results show that, at these dosages, the 24 h urinary iodine values are above baseline for both oral and intramuscular administrations (im: >12 months/oral: 6 months) for prolonged period of time. In terms of safety, Lipiodol, administered by im injection or orally, did not induce any undesirable effects or any alteration of thyroid function tests in this study., Conclusions: In conclusion, this study shows that im or oral administration of a single dose of Lipiodol provides a significant and prolonged iodine supplement. The results obtained confirm the possibility of protection of exposed populations after annual administration of an appropriate single oral dose, without inducing any clinical or laboratory adverse effects. The product, by either route of administration, has a prolonged efficacy in iodine-deficient subjects (im: 2-3 years/oral: 1 year).

Background: Boron neutron capture therapy (BNCT) is a form of radiation therapy and has been proposed for the treatment of some malignancies with encouraging results. However, none of them has ever been applied to liver malignancy. The purpose of this study was to evaluate the potential of boron-lipiodol (B-lipiodol) for the treatment of VX2 liver tumor via BNCT., Materials and Methods: Twelve New Zealand rabbits were randomly separated into two groups: lipiodol and boron-lipiodol groups. The rabbits were anesthetized, a midline incision was made and the left lobe of the liver was injected with 0.1 ml of VX2 tumor cells. After the tumor reached 2-3 cm in diameter, the rabbits were anesthetized and 0.5 ml of boron-lipiodol was injected into the hepatic artery via an angiocatheter. Liver function tests and renal function tests were performed before, at 12 hours, 24 hours, 48 hours and 7 days after injection of drugs in both groups. The concentration of boron in various tissues was determined on the 7th day after injection., Results: Liver function was abnormal at 12 hours after injection, and then gradually returned to normal at 7 days, indicative of acute temporary hepatic damage. As for the renal function, no significant change was noted in either group. The boron level was 49.7 ppm in tumor and 6.31 ppm in the healthy liver 7 days after injection of B-lipiodol. The ratio of boron concentrations between the tumor and the normal liver tissue was 7.87. As for blood and other organs including spleen, heart and kidney, the concentration of boron was low. In the lipiodol group, the boron concentrations in tumor and various organs were low., Conclusion: The high concentration of boron after intra-arterial injection of B-lipiodol can be used for neutron capture therapy. B-lipiodol has potential for the treatment of liver malignancy.

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before (131)I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after (131)I-lipiodol ( n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry ( n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 ( n=17) or 4 ( n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity ( n=31) compared with 0.42%+/-0.20% in the non-KI group ( n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group ( n=19) versus 11.9+/-5.9 Gy in the non-KI group ( n=21). These differences were statistically significant ( P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident ( P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Background: Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture., Methods: Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy., Results: Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells., Conclusion: Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.

Radioisotope-labelled lipiodol has been used in the therapy of liver cancer. Recently a lipiodol solution of 188Re-labelled diaminedithiol (DD) has been reported to show a high uptake in the liver cancer. We synthesized long-chain alkyl DD derivatives to improve their uptake and retention in tissue. As the length of the alkyl chain increased, tissue uptake and retention also increased due to hydrophobic interaction with lipiodol. Among the synthesized compounds, the lipiodol solution of 188Re-HDD, the DD derivative with the longest side chain (C16), is a promising agent for therapy of liver cancer.

In the developing countries of Africa, many children are at high risk for both goiter and iron-deficiency anemia (IDA). Because iron (Fe) deficiency can have adverse effects on thyroid metabolism, Fe deficiency may influence response to supplemental iodine in areas of endemic goiter. Therefore, our aims were to determine: 1) if goitrous children also suffering from IDA could respond to oral iodine supplementation; and 2) if Fe supplementation in goitrous children with IDA would improve their response to oral iodized oil and iodized salt. First, we compared the efficacy of oral iodized oil in two groups of goitrous children: a nonanaemic group vs. an IDA group. The therapeutic response to iodized oil was impaired in the goitrous children with IDA. Second, an open trial of Fe treatment in goitrous children with IDA improved their response to oral iodized oil. Finally, in a randomized double-blind trial, goitrous, Fe-deficient children consuming iodized salt were given Fe supplementation or placebo. Fe supplementation improved the efficacy of the iodized salt. In these studies, both anatomic (thyroid size) and biochemical (TSH, T4) measures indicated that iodine significantly improved thyroid function in the nonanaemic children compared to the Fe deficient children. Iodine was less efficacious in children with lower Hb at baseline and in those with a poorer response to Fe. The data suggest that a high prevalence of IDA among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis.

Lipiodol is taken up by hepatocellular carcinomas and is used for diagnosis and therapy. This is the first report of lipiodol uptake by liver metastases from breast cancer.

Thyroid complications resulting from excess iodide such as thyrotoxicosis, thyroiditis, sialadenitis, or hypothyroidism are much rarer after iodine supplementation with Lipiodol than with KI. They do not militate against its widespread use in endemic goiter populations, especially in pregnant women. However, patients with multinodular goiter should not be treated or should be treated only under careful observation. When Lipiodol-induced thyrotoxicosis occurs it tends to be mild or even subclinical and self-limited. If treatment is required, potassium perchlorate with or without thionamides is recommended. Iodide goiter has not been seen after Lipiodol supplementation, nor has thyroiditis. Sialadenitis occurs rarely. Iodide derived from Lipiodol readily enters the fetus, possibly by active transport, and theoretically endangers the fetus because autoregulation of the fetal thyroid occurs late during gestation. Despite the difficulty in distinguishing iodide goiter from iodide deficiency goiter of the newborn, no cases of neonatal iodide goiter have been reported. Possible mechanisms of thyroid inhibition by excess iodide are briefly discussed. The use of locally produced iodized plant oils is recommended for financial reasons as well as for the benefits derived from local participation.

Purpose: To investigate the effect of starvation on contrast-enhanced CT of the liver using the iodinated hepatocyte-specific lipid emulsion FP 736-04., Material and Methods: CT examination of the liver was performed in Sprague-Dawley rats before and after an i.v. infusion of 1.0 ml/kg b.w. of FP 736-04. The examination was preceded by a 15-h period of food withdrawal (the starvation group). A control group was subjected to the same CT examination protocol with use of FP 736-04 but without prior starvation., Results: Liver attenuation values did not differ significantly between the starvation and the control group (p>0.05)., Conclusion: A pre-examination period of starvation had no effect on FP 736-04 liver enhancement on CT However, liver attenuation tended to decrease more slowly in the starvation group than in the controls.

The ileal uptake of polyalkylcyanoacrylate nanocapsules (less than 300 nm in diameter) has been investigated in the rat. Iodised oil (Lipiodol) was used as the tracer for X-ray microprobe analysis in scanning electron microscopy. Lipiodol nanocapsules, or an emulsion of Lipiodol, were administered in the lumen of an isolated ileal loop of rat. Lipiodol nanocapsules improved the absorption of the tracer as indicated by increased concentrations of iodine in the mesenteric blood (+27%, P < 0-01, compared with Lipiodol emulsion). Intestinal biopsies were taken at different time points and the samples underwent cryofixation and freeze-drying. The nanocapsules were characterized by their strong iodine emission, and electron microscopy of the biopsy samples revealed nanocapsules in the intraluminal mucus of the non-follicular epithelium, then in the intercellular spaces between enterocytes, and finally the nanocapsules were found within intravillus capillaries. However, nanocapsules were most abundant in the Peyer's patches, where the intestinal epithelium had been crossed by way of the specialized epithelial cells, designated membranous cells, or M cells, and their adjacent absorptive cells. These observations were confirmed quantitatively by measuring iodine concentrations in the various tissue compartments. Ten minutes after the intraluminal administration of Lipiodol nanocapsules, the emission of iodine peaked in the mucus (+77%, P < 0.01), in M cells (+366%, P <0.001), in enterocytes adjacent to M cells (+70%, P < 0.05) and in lymph vessels (+59%, P < 0.05). Polyalkylcyanoacrylate nanocapsules were able to pass through the ileal mucosa of the rat via a paracellular pathway in the non-follicular epithelium, and most predominantly, via M cells and adjacent enterocytes in Peyer's patches.

Aims: 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., Methods: 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., Results: 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., Conclusions: 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.

A case of transitional cell carcinoma of the bladder with symptomatic liver metastases is presented. When conventional chemotherapy failed, a lipiodol CT scan demonstrated avid uptake by the tumours, which has implications for targeted cancer therapy.

Oral supplementation with iodized oil for correction of iodine deficiency in a population has advantages over intramuscular injection but the duration of effect is shorter. The relation of intestinal parasite treatment and efficacy of oral iodized oil was examined in an intervention study in 8-10-y-old schoolchildren in Malawi. Severely iodine-deficient schoolchildren with a single parasitic infestation of Ascaris lumbricoides (n = 44), hookworm (n = 42), or Entamoeba histolytica (n = 24) were randomly allocated to receive or not receive treatment before taking a 1-mL oral supplement (490 mg I) of iodized ethyl esters from poppy seed oil. The urinary iodine concentration was measured at various time points after supplementation to define the time intervals before urinary iodine concentrations returned to 0.40 mumol/L, indicating moderate iodine deficiency. Treatment with metronidazole for E. histolytica increased the protection period from 2.0 to 21.0 wk (P < 0.05). For all untreated children together, the duration of effect was 9.2 wk shorter (P < 0.001) than that for their treated peers (16.8 wk). We conclude that intestinal parasitic infestations reduce the efficacy of oral supplementation with iodized ethyl esters by interfering with absorption.

Background: Age is considered one of the important contraindications to surgery for hepatocellular carcinoma (HCC) in cirrhosis patients. We therefore evaluated the safety and prevalence of side effects in endoarterial therapy (EAT) in subjects aged over 65 years compared with younger treated patients., Methods: Thirty-eight patients with HCC aged 65 years and over underwent transcatheter arterial chemoembolization (TACE) (n = 28) or intraarterial chemotherapy (IAC) (n = 10). The survival rate was calculated using Kaplan-Meier's method with respect to a control group consisting of younger treated subjects (44 TACE; 21 IAC) comparable for stage of HCC and severity of the underlying cirrhosis., Results: The comparison between the two groups regarding side effects, procedure-related death, and survival did not show any difference considering the whole EAT procedure. TACE in elderly subjects reached a statistically lower outcome with respect to younger patients (p < .025) but remained statistically superior in survival versus both older and younger patients treated with IAC (p < .05, respectively). Stratifying the patients following the degree of Lipiodol uptake of tumor mass in the three groups (Group I, > 75%; Group II, 50-75%; Group III, < 50%), in the young subjects a higher probability of survival was strictly correlated to a degree of uptake over 75%, while in the elderly patients an impregnation over 50% was sufficient to obtain a satisfactory survival curve., Conclusions: EAT is a reliable and safe therapeutic option for the geriatric patient with HCC, with TACE showing a better efficacy than IAC, requiring a lesser degree of Lipiodol uptake to achieve an improvement of outcome.

Purpose: To investigate whether liver uptake of the iodinated hepatocyte-specific lipid emulsion FP 736-04 is altered by fatty infiltration of the liver., Material and Methods: Fatty infiltration of the liver was induced in female Sprague-Dawley rats by an intraperitoneal injection of L-ethionine preceded by 15 h of food withdrawal. CT of the liver was performed before and 24 h after the administration of L-ethionine and, in addition at the latter time point, after an i.v. injection of 1.0 ml/kg b.w. of FP 736-04. A control group was subjected to the same CT examination protocol., Results: Intraperitoneal administration of L-ethionine caused liver steatosis, as established by liver triglyceride analysis, leading to a significant decrease in the liver attenuation, from 69.2 +/- 2.4 to 27.8 +/- 12.0 HU. The uptake of FP 736-04 by the fatty liver was significantly reduced, yielding a maximum enhancement of 22.3 +/- 7.9 HU as compared to a value of 32.3 +/- 5.0 HU in the control group., Conclusion: Enhancement by FP 736-04 was reduced in the steatotic liver compared with the normal liver. It remains to be established whether this degree of enhancement is sufficient for reliable lesion detection.

Purpose: The aim of the study was to investigate whether moderately to well differentiated hepatocellular carcinomas (HCC) possess the same ability to take up a new lipid emulsion contrast medium, FP 736-03, as do hepatocytes., Material and Methods: A rat model of an experimental HCC was used. CT was performed before and after an i.v. bolus injection of 1.0 ml FP 736-03/kg b.w. Attenuation values of normal liver parenchyma and tumour tissue were measured over time., Results: The contrast medium was taken up by the normal liver parenchyma but not by the tumour tissue for which the attenuation remained virtually constant over the observation period., Conclusion: The study demonstrated that FP 736-03 was not taken up by the HCC, thus producing a high lesion-to-liver contrast.

To clarify the optimal dose of Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France) during Lipiodol-transcatheter arterial embolization (L-TAE) and segmental L-TAE used to treat hepatocellular carcinoma, we studied the relationship between the volume of Lipiodol used during these procedures and the necrosis rates in resected specimens, as well as the correlation with the Lipiodol accumulation pattern based on the computed tomography findings (L-CT) and the volume of Lipiodol in resected and nonresected cases after L-TAE or segmental L-TAE. The L-CT and the dose of Lipiodol injected (mL) were studied correlatively in 198 cases (28 resected cases and 170 nonresected cases; tumor size < or = 5 cm in 52 cases and > 5 cm in 118 cases) that underwent L-TAE and in 80 cases (14 resected cases and 66 nonresected cases, tumor size < or = 5 cm in 52 cases and > 5 cm in 14 cases) that underwent segmental L-TAE. The L-CT was classified into four types: type I, homogeneous accumulation (type Ia, accumulation around the tumor; type Ib, no accumulation around the tumor); type II, partial defect; type III, sporadic accumulation; and type IV, punctate or no accumulation. In the 42 resected cases (L-TAE, 28 cases; segmental L-TAE, 14 cases), type I was seen in 68% (Ib, 100%) of the L-TAE cases and 93% (Ia, 79%; Ib, 14%) of the segmental L-TAE cases. The necrosis rate of the cases with type Ib L-CT was 90% to 100%, and all type Ia cases showed complete necrosis. In the 236 nonresected cases (L-TAE, 170 cases; segmental L-TAE, 66 cases), the volume of Lipiodol injected correlated with the L-CT type. In the L-TAE cases with a tumor size < or =5 cm, the frequency of the injected Lipiodol volume (D) being greater than the tumor diameter (d) (D > or = d) was 90%, and 87% of the cases with D > or = d showed type Ib L-CT. In the group whose tumor diameter (d) was more than 5 cm, the frequency of D > or = d was 25%, and 70% of the cases of D > or = d were type Ib. The frequency of D < d was 75%, and in 13% of these cases the L-CT was type Ib and the maximum dose was approximately 10 mL. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, the frequency of D > or = d was 83%, and 93% of those cases showed type I, including 85% of type Ia. There was a correlation between the L-CT type and the necrosis rate, and type I, especially Ia in segmental L-TAE, showed complete necrosis in almost all cases. In L-TAE, standards for the optimal dose of Lipiodol are thought to be as follows: D > or = d in cases with d < or = 5, and slightly D < d and 10 mL maximally in cases with d > 5. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, enhancement of the therapeutic effect was seen compared with L-TAE. This is surmised to have been because of the higher Lipiodol volume with anticancer agents per unit volume of the tumor in segmental L-TAE.