Optimal scan timing of hepatic arterial-phase imaging of hypervascular hepatocellular carcinoma determined by multiphasic fast CT imaging technique.

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.

Experimental assessment of temperature influence on miriplatin and cisplatin iodized-oil suspension viscosity.

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.

Iodinated nano-emulsions as contrast agents for preclinical X-ray imaging: Impact of the free surfactants on the pharmacokinetics.

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.

Utilisation of iodine from different sources by sows and their progeny.

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.

Preparation of 177Lu-labeled oxine in lipiodol as a possible agent for therapy of hepatocellular carcinoma: a preliminary animal study.

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.

Pattern and chronological change of iodized oil retention in radiofrequency ablation-induced vascular injury area: differentiation from iodized oil retention in recurrent hepatocellular carcinoma on computed tomography.

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.

Effect of sodium thiosulfate on cisplatin removal after intra-arterial embolization with a lipiodol-platinum suspension for hepatocellular carcinoma.

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.

Biodistribution of phenylboric acid derivative entrapped lipiodol and 4-borono-2-18F-fluoro-L-phenylalanine-fructose in GP7TB liver tumor bearing rats for BNCT.

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.

Preparation and evaluation of 99mTc(CO)3-labeled pentadecanoic acid derivative and its suspension in lipiodol.

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.

Preparation of 166Ho-oxine-lipiodol and its preliminary bioevaluation for the potential application in therapy of liver cancer.

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.

Retention of lipiodol after parotid gland sialography.

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.

Development of acetylated HDD kit for preparation of 188Re-HDD/lipiodol.

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.

ZT glue immobilizes iodinated oil in vivo.

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.

[Plasma platinum concentration and anti-tumor effects after intra-arterial infusion of lipiodol-CDDP suspension evaluation with VX 2 rabbit liver cancer model and 7.0 Tesla MRI system].

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.

Transarterial ethanol ablation of cirrhotic liver with lipiodol-ethanol mixture: safety and efficacy study in rats.

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.

(188)Re-HDD/lipiodol therapy for hepatocellular carcinoma: an activity escalation study.

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.

Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats.

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.

188Re-HDD/lipiodol therapy for hepatocellular carcinoma: a phase I clinical trial.

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.