Intrahepatic Activity Distribution in Radioembolization with Yttrium-90-Labeled Resin Microspheres Using the Body Surface Area Method--A Less than Perfect Model.

PURPOSE: To retrospectively assess the influence of the parameters of the body surface area (BSA) method in hepatic radioembolization using yttrium-90-labeled microspheres on the determination of the prescribed activity. MATERIALS AND METHODS: Data from 283 consecutive patients treated with radioembolization (BSA method) were included. For interindividual comparisons, activity concentrations (ACs; MBq/mL) were calculated for each liver. The impact of the BSA method parameters was assessed by analysis of variance and pairwise t test with Bonferroni-Holm correction. RESULTS: Prescribed activity was 1.01-2.71 GBq, with BSA, liver volume (LV), tumor burden, and the liver-lung shunt reduction factor (LLS RF) being significant contributing factors to the AC (all P < .0001, analysis of variance). BSA and LV correlated only moderately (ρ = 0.46, P < .0001). Compared with base activity defined by the BSA (median = 1.67 GBq; range, 1.20-2.32 GBq), the activity contribution of tumor burden was small (median = 150 MBq; range, 3-800 MBq). Resulting activities were reduced according to LLS RF by 20% in 12.4% and by 40% in 3.5% of patients. AC was significantly (up to 56%) lower in association with larger LV than in small LV (LV < 1,500 mL vs ≥ 2,500 mL, P < .0001). CONCLUSIONS: In the BSA model, BSA and LV showed only a moderate correlation, resulting in a significantly lower AC in patients with larger livers. Tumor burden percentage contributed little to the prescribed activity because the BSA model did not account for actual LVs and tumor volumes. These inaccuracies may potentially result in underdosage in patients with larger livers, especially if further LLS RF needs to be applied.

Prospective comparison of hydrogel-coated microcoils versus fibered platinum microcoils in the prophylactic embolization of the gastroduodenal artery before yttrium-90 radioembolization.

PURPOSE: To prospectively assess the performance of hydrogel-coated versus fibered microcoils in the prophylactic occlusion of the gastroduodenal artery (GDA) before yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: A total of 43 patients were randomized to receive fibered microcoils (n = 15), detachable hydrogel-coated microcoils (n = 13), or pushable hydrogel-coated microcoils (n = 15). Numbers of coils used, duration, dose-area product (DAP), contrast agent load, and coil migration were assessed. At the time of yttrium-90 ((90)Y) radioembolization, persistent GDA occlusion was analyzed. RESULTS: In all patients, the embolized GDA was still completely occluded at the time of (90)Y radioembolization. Mean numbers of microcoils used per patient were 11.5 (fibered microcoils), 2.9 (detachable hydrocoils), and 5.5 (pushable hydrocoils), with all numbers significantly different (P<.0001). Mean DAPs were 16,283 mGy/cm(2)±16,545 (standard deviation) for fibered microcoils, 13,786 mGy/cm(2)±5,990 for detachable hydrocoils, and 35,757 mGy/cm(2)±74,493 for pushable hydrocoils (P = .87). Mean durations of GDA coil embolization were 20 minutes for fibered microcoils, 25 minutes for detachable hydrocoils, and 32 minutes for pushable hydrocoils (P = .0015). Mean contrast agent loads were 9 mL for fibered microcoils, 11 mL for pushable hydrocoils, and 7 mL for detachable hydrocoils (P = .13). One case of coil migration occurred with each type. CONCLUSIONS: Hydrogel-coated and fibered microcoils are equally effective for prophylactic occlusion of the GDA before radioembolization. The number of coils used is higher with fibered microcoils compared with pushable and detachable hydrocoils, but the reduced number of hydrocoils comes at the cost of increased procedure duration.

Monte Carlo characterization of biocompatible beta-emitting 90Y glass seed incorporated with the radionuclide 153Sm as a SPECT marker for brachytherapy applications.

A glass seed consisting of the ß--emitting radionuclide 90Y incorporated with radionuclide 153Sm as SPECT marker is proposed for potential application in brachytherapy in order to reduce the undesirable dose to healthy adjacent organs. The aim of this work is to determine the dosimetric characteristics, as suggested in the AAPM TG-60/TG-149 reports, for this seed using Monte Carlo simulation. Monte Carlo codes MCNP5, EGSnrc, and FLUKA were used to calculate the absorbed dose distribution around the seed. Dosimetric parameters, such as reference absorbed dose rate, radial dose function, and one-dimensional (1D) and two-dimensional (2D) anisotropy functions, were obtained. The computational results from these three codes are in agreement within 5.4% difference on average. The absorbed dose rate at the reference point was estimated to be 5.01 cGy h-1 µCi-1 and self absorption of YAS glass seed amounted to 30.51%. The results showed that, with thermal neutron bombardment of 5 hours in a typical flux, sufficient activity for applications in brachytherapy may be achieved. With a 5 mCi initial activity, the total dose of a YAS glass seed was estimated to be 1.38 Gy at 1.0 cm from the seed center. Comparing with gamma emitting seeds, the 90Y seed could reduce undesirable doses to adjacent organs, because of the rapid dose falloff of beta ray. Because of the high R90 value of 5.5 mm, fewer number of 90Y seeds will be required for an interstitial brachytherapy treatment using permanent implant, in comparison with other beta-emitting seeds. The results would be helpful in the development of the radioactive implants using 90Y glass seeds for the brachytherapy treatment.

Super selective radio embolization of the porcine kidney with 90yttrium resin microspheres: a feasibility, safety and dose ranging study.

PURPOSE: We determined whether super selective radio embolization of the porcine kidney was technically feasible and evaluated histopathological changes in the treatment target zone (upper or lower renal pole), adjacent nontargeted kidney, and adjacent and distant organs after administering (90)Y labeled vs bland resin microspheres. MATERIALS AND METHODS: We performed super selective radio embolization with (90)Y resin microspheres in 1 kidney and with an equivalent number of bland microspheres in the corresponding pole of the contralateral kidney as a control. The aim was to achieve radio embolization of a target zone equivalent to approximately a third of the kidney volume. A pathologist independently graded macroscopic and microscopic changes in the kidney, and adjacent and distant tissue resulting from incremental increases (0.15 to 0.35 GBq) in implanted activity in 6 pigs. RESULTS: We recorded grade 4 histological changes in the treatment target zone (upper or lower renal pole) in 5 of 6 pigs after injecting (90)Y resin microspheres with evidence of nephron sparing effects in the adjacent renal tissue at the lowest activity. At activity greater than 0.3 GBq increasing damage was noted to adjacent renal tissue beyond the treatment target zone. No toxicity was evident in adjacent or distant organs. CONCLUSIONS: Delivery of highly targeted intra-arterial radiotherapy to the kidney is feasible and safe in the pig model. Further evaluation is warranted as a potential treatment for advanced renal cell carcinoma or for localized disease in patients who are not candidates for surgery.

Dose-response for yttrium-90 resin microsphere radioembolisation.

The fundamental premise of yttrium-90 radioembolisation is to balance safety with efficacy. To achieve this, dose-response guidance must be provided. This is a tabulation of published data of key dose-response metrics for yttrium-90 resin microsphere radioembolisation of liver malignancies. Metrics are expressed in terms of mean radiation absorbed doses (Gy), dose-volume histograms, Biologically Effective Doses, Normal Tissue Complication Probability and Tumour Control Probability.

Radiation Safety for Yttrium-90-polymer Composites (RadioGel™) in Therapy of Solid Tumors.

ABSTRACT: Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite comprises insoluble, microscopic yttrium-phosphate particles carried by a sterile, injectable water-polymer (hydrogel) solution that can be placed directly by needle injection into solid tumors. The yttrium-90-RadioGel™ agent was designed to provide a safe, effective, localized, high-dose beta radiation for treating solid tumors. The properties of 90Y-RadioGel™ also make it a relatively safe agent for health care personnel who prepare, handle, and administer the material. The purpose of this work was to demonstrate and characterize radiation safety of the injectable 90Y-RadioGel™ therapeutic agent. Safety in the patient is defined by its ability to target precisely and remain confined within tumor tissue so that radiation doses are imparted to the tumor and not to normal organs and tissues. Radiation safety for health care personnel is defined by the low radiation doses received by persons who prepare and administer the agent. These safety features were demonstrated during experiments, first involving laboratory rabbits and second in cat and dog animal patients that were treated clinically for sarcoma tumors. This paper focuses mainly on the rabbit tissue biodistribution study; follow-on clinical application in cat and dog subjects confirmed the rabbit results. Implanted VX2 liver tumors in the hind limbs of 26 New Zealand White rabbits were treated using tracer amounts of either (a) 90Y-RadioGel™ or (b) 90Y-microparticles in phosphate-buffered saline (PBS) without the gel carrier. Tumor and margin injections were interstitial. Rabbits were euthanized at 48 h or 10 d following injection. Blood and tissues (tumor or tumor margins, liver, lymph nodes, rib bone, kidney, spleen) were collected for liquid scintillation counting using wet-ash procedures. Biodistribution was also analyzed at 10 d post-injection using micro-computed tomography. Thirteen cat and dog subjects were also treated clinically for sarcomas. Liquid scintillation counting at 48 h post-injection of tumors or margins with 90Y-RadioGel™ showed that significant radioactivity was measurable only at the site of administration and that radioactivity above detector background was not found in blood or peripheral organs and tissues. At 10 d post-injection, microCT showed that yttrium phosphate microparticles were confined to the injection site. Yttrium-90 remained where placed and did not migrate away in significant amounts from the injection site. Radiation doses were confined mainly to tumors and margin tissues. During preparation and administration, radiation doses to hands and body of study personnel were negligible. This work showed that 90Y-RadioGel™ can be safely prepared and administered and that radiation doses to cancer patients are confined to tumor and margin tissues rather than to critical normal organs and tissues.

Biodegradable 131 Iodine-Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment.

Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg-1 of microspheres as well as favorable stability in vitro. Then, 131 I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of 131 I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I-CCMs treatment. In conclusion, these biodegradable 131 I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.

Simultaneous Time-of-Flight PET/MR Identifies the Hepatic 90Y-Resin Distribution After Radioembolization.

A 61-year-old woman with multiple hepatic metastases from uterus cervical cancer received Y radioembolization. The simultaneous time-of-flight (TOF) PET/MR clearly identified the untreated tumor parts on the posttherapeutic Y internal pair-production imaging. After another boosted Y injection, the metastatic hepatic tumors were well covered. The follow-up PET/MR revealed tumor shrinkage. The one-stop-shop TOF PET/MR provided useful follow-up information in patients receiving Y radioembolization.

Beta emitters and radiation protection.

BACKGROUND: Beta emitters, such as (90)Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding. AIM: To discuss practical precautions for handling beta emitters in general, and specifically determine proper shielding for (90)Y, while comparing to (177)Lu and (131)I. The aim is achieved through the application of physical principles combined with results from practical experience. MATERIAL AND METHODS: Typical and maximal electron ranges were calculated for (131)I, (177)Lu, and (90)Y, using data from a freely available database. Bremsstrahlung yields were calculated for (90)Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from (90)Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons preparing (90)Y-Zevalin were measured. CONCLUSIONS: Good laboratory practice is important to keep radiation doses low. To reduce bremsstrahlung, (90)Y should not be shielded by lead but instead perspex (10 mm) or aluminium (5 mm). Bremsstrahlung radiation can be further reduced by adding a millimetre of lead on the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure.

The use of gel dosimetry to measure the 3D dose distribution of a 90Sr/90Y intravascular brachytherapy seed.

Absorbed dose distributions in 3D imparted by a single (90)Sr/(90)Y beta particle seed source of the type used for intravascular brachytherapy were investigated. A polymer gel dosimetry medium was used as a dosemeter and phantom, while a special high-resolution laser CT scanner with a spatial resolution of 100 microm in all dimensions was used to quantify the data. We have measured the radial dose function, g(L)(r), observing that g(L)(r) increases to a maximum value and then decreases as the distance from the seed increases. This is in good agreement with previous data obtained with radiochromic film and thermoluminescent dosemeters (TLDs), even if the TLDs underestimate the dose at distances very close to the seed. Contrary to the measurements, g(L)(r) calculated through Monte Carlo simulations and reported previously steadily decreases without a local maximum as a function of the distance from the seed. At distances less than 1.5 mm, differences of more than 20% are observed between the measurements and the Monte Carlo calculations. This difference could be due to a possible underestimation of the energy absorbed into the seed core and encapsulation in the Monte Carlo simulation, as a consequence of the unknown precise chemical composition of the core and its respective density for this seed. The results suggest that g(L)(r) can be measured very close to the seed with a relative uncertainty of about 1% to 2%. The dose distribution is isotropic only at distances greater than or equal to 2 mm from the seed and is almost symmetric, independent of the depth. This study indicates that polymer gel coupled with the special small format laser CT scanner are valid and accurate methods for measuring the dose distribution at distances close to an intravascular brachytherapy seed.

Salvage radioembolization of liver-dominant metastases with a resin-based microsphere: initial outcomes.

PURPOSE: The use of radioembolization of hepatic metastases with yttrium-90 ((90)Y) microspheres is increasing. The present report describes the outcomes in a cohort of patients with metastatic liver tumors treated with a resin-based microsphere agent. MATERIALS AND METHODS: Thirty patients with colon (n = 13), breast (n = 7), and other primary cancers (n = 10) were treated after the failure of first- and second-line therapy. Overall survival (OS), time to progression (TTP), and time to treatment failure (TTTF) were calculated from the first treatment. Response was measured according to Response Evaluation Criteria In Solid Tumors at interval follow-up imaging. RESULTS: Thirty patients underwent 56 infusions of (90)Y, and 18 remained alive at the end of the study. Fourteen patients (47%) had a partial response or stable disease. OS (604 vs 251 days), TTP (223 vs 87 days), and TTTF (363 vs 87 days) were all significantly longer for patients who had a partial response or stable disease (P < .05). Median OS, TTP, and TTTF for patients with colorectal carcinoma were 357, 112, and 107 days, respectively, versus 638, 118, and 363 days in patients with other metastatic sources. Median survival was not reached for patients with breast carcinoma, and the TTP and TTTF were each 282 days. One patient (3%) experienced grade 3 toxicity (gastrointestinal ulceration). CONCLUSIONS: (90)Y microsphere therapy produced promising survival rates compared with systemic salvage options, with minimal toxicity.

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres.

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.

90Y radioembolization dosimetry using a simple semi-quantitative method in intrahepatic cholangiocarcinoma: Glass versus resin microspheres.

INTRODUCTION: There are two different types of 90Y Microspheres, glass and resin, in the market for 90Y radioembolization (90Y-RE). This study aimed to investigate the dose of radiation delivered through glass vs. resin-based 90Y-RE to intrahepatic cholangiocarcinoma (ICC). METHODS: In this retrospective study, 10 patients with ICC underwent 90Y-RE, five underwent glass (Glass group) and other 5 resin (Resin group) microspheres. Technetium-99m macro-aggregated albumin (Tc-99m MAA) shunt study was performed two weeks before 90Y-RE. Within 2 h from 90Y-RE, Bremsstrahlung SPECT/CT was obtained. Regions of interest (ROIs) were segmented around the targeted tumor and the liver. Tumor and liver volumes, corresponding radioactive counts, and tumor to liver count ratio were calculated using MIM software and compared between Glass and Resin groups. RESULTS: Mean hepatopulmonary shunt fraction was 7.1 vs. 6.2% for the Glass and Resin groups (p = 0.83), with no extrahepatic activity. There was no difference in the activity and tumor uptake of administered Tc-99m MAA between both groups (p = 0.71 and p = 0.63). Mean administered activity of 90Y in the Glass group was higher than the Resin group (73.2 ±â€¯24.3 vs. 44.5 ±â€¯18.2 mCi, p < 0.001). The tumor 90Y uptake was significantly higher in the Glass group compared to the Resin group (41.3% vs. 33.5%, p < 0.001), corresponding to the mean tumor dose of 205.7 ±â€¯19.7 vs. 128.9 ±â€¯10.6 Gy, respectively (p < 0.001). The tumor to normal liver parenchyma 90Y dose ratio was significantly higher in the Glass group compared to the Resin group, 4.9 ±â€¯0.7 versus 2.4 ±â€¯0.3 respectably (p < 0.001). CONCLUSIONS: Both 90Y glass and resin-based microsphere 90Y-RE are feasible and safe in patients with ICC, while 90Y glass microsphere delivers higher dose of 90Y to the targeted tumors. ADVANCES IN KNOWLEDGE: While both 90Y glass and resin-based microsphere yttrium-90 radioembolization are feasible and safe treatment options for in patients with intrahepatic cholangiocarcinoma, 90Y glass microsphere delivers higher dose of 90Y to the targeted tumors. IMPLICATIONS FOR PATIENT CARE: Both of 90Y glass and resin-based microsphere can be safely and feasibly used for treatment of intrahepatic cholangiocarcinoma, difference in dose of 90Y delivered to the targeted tumors should be clinically considered while choosing the microsphere type.

Radiotherapy of CD45-expressing Daudi tumors in nude mice with yttrium-90-labeled, PEGylated anti-CD45 antibody.

Studies were performed to determine the suitability of using the polyethylene glycol (PEG)-labeled AHN-12 anti-CD45 monoclonal antibody to deliver the high-energy beta-particle-emitting isotope 90Y to a CD45+ B-cell Daudi lymphoma grown as flank tumors in athymic nude mice. The PEGylated radiolabeled antibody displayed a significantly better antitumor effect in the mouse tumor flank model (p<0.03) and significantly better blood pharmacokinetics in normal rats (p<0.05) than the non-PEGylated radiolabeled antibody. Studies of two different sizes of PEG showed that rats given 43 kDa of PEGylated AHN-12, but not 5 kDa of PEGylated AHN-12, had significantly higher radiolabeled antibody blood levels and, therefore, improved pharmacokinetics, as compared to rodents given non-PEGylated radiolabeled AHN-12 (p<0.05). Surviving mice revealed no signs of kidney, liver, or gastrointestinal damage by histology study. Notably, in vitro studies indicated that PEGylation did not have a major effect on labeling efficiency and the binding of labeled antibody. These findings indicate that PEGylation of radiolabeled anti-CD45 antibody may be a useful and desirable means of extending blood half-life and enhancing efficacy. Also, the final outcome may be impacted by the size of the PEG molecule used for the modification of the blood half-life.

Resin Versus Glass Microspheres for 90Y Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma Using Pretreatment Partition Model Dosimetry.

The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with 90Y transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). Methods: We performed a retrospective analysis of prospectively collected data on 77 patients consecutively treated (mean age ± SD, 66.4 ± 12.2 y) for uHCC (36 uninodular, 5 multinodular, 36 diffuse) with 90Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size, and serum α-fetoprotein (AFP) level were investigated using Cox proportional hazards regression. Results: The characteristics of 2 groups were comparable with regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level, and 90Y global administered activity. The median follow-up time was 7.7 mo (range, 0.4-50.1 mo). Relapse occurred in 44 patients (57%) at a median of 6 mo (range, 0.4-27.9 mo) after 90Y TARE, and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed higher but not statistically significantly PFS and OS rates in the 90Y resin group than the 90Y glass group (resin PFS 6.1 mo [95% confidence interval CI, 4.7-7.4] and glass PFS 5 mo [95% CI, 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI, 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of 90Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated, Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after 90Y TARE. Conclusion: Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with 90Y TARE using pretreatment PMD. Further, larger prospective studies are warranted to confirm these findings.

Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: a feasibility study in pigs.

BACKGROUND: Internal radiotherapy requires the localization of the radionuclide to the site of action. A new injectable alginate gel formulation intended to undergo immediate gelation in tissues and capable of encapsulating radioactive particles containing 90Y was investigated. METHODS: The formulation was injected intramuscularly, into the bone marrow compartment of the femur and intravenously, respectively, in pigs. The distribution of radioactivity in various tissues was determined. RESULTS: Following intramuscular injection, more than 90% of the radioactivity was found at the site of injection. Following injection into bone marrow, 30-40% of the radioactivity was retained at the site of injection, but a considerable amount of radioactivity was also detected in the lungs (35-45%) and the liver (5-18%). Following intravenous injection, 80-90% of the radioactivity was found in the lungs. CONCLUSION: The present formulation appears suitable for localized radiotherapy in organs and tissues having low perfusion.

Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells.

Radiolabeled antibodies have produced encouraging remissions in patients with chemotherapy-resistant hematological malignancies; however, the selection of therapeutic radionuclides for clinical trials remains controversial. In this study, we compared the internalization, lysosomal targeting, metabolism, and cellular retention of radiolabeled murine and humanized monoclonal antibodies targeting the CD33 antigen (monoclonal antibodies mP67 and hP67, respectively) on myeloid leukemia cell lines (HEL and HL-60) and of anti-carcinoma antibodies (monoclonal antibodies hCTM01 and hA33) targeting breast cancer and colorectal carcinoma cell lines (MCF7 and Colo 205, respectively). Each antibody was labeled with 125I (by the IodoGen method) and with 111In and 90Y using macrocyclic chelation technology. Targeted tumor cells were analyzed for retention and metabolism of radioimmunoconjugates using cellular-radioimmunoassays, Percoll gradient fractionation of cell organelles, SDS-PAGE, and TLC of cell lysates and culture supernatants. Our results suggest that antibodies are routed to lysosomes after endocytosis, where they are proteolytically degraded. [125I]monoiodotyrosine is rapidly excreted from cells after lysosomal catabolism of antibodies radioiodinated by conventional methods, whereas small molecular weight 111In and 90Y catabolites remain trapped in lysosomes. As a consequence of the differential disposition of small molecular weight catabolites, 111In and 90Y conjugates displayed superior retention of radioactivity compared with 125I conjugates when tumor cells were targeted using rapidly internalizing antibody-antigen systems (e.g., hP67 with HEL cells and hCTM01 with MCF7 cells). When tumor cells were targeted using antibody-antigen systems exhibiting slow rates of endocytosis (e.g., hP67 on HL-60 cells and hA33 on Colo 205 cells), little differences in cellular retention of radioactivity was observed, regardless of whether 125I, 111In, or 90Y was used.

A descriptive analysis of remnant activity during (90)Y resin microspheres radioembolization of hepatic tumors: technical factors and dosimetric implications.

OBJECTIVE: Activity planning for (90)Y radioembolization aims to maximize the effect of the treatment while keeping toxicity acceptably low. Our aim was to describe the amount of residual activity in post-treatment v-vials and tubing and analyze the possible factors affecting it (total activity administered, number of split activity injection(s), previous treatments, administration artery and microcatheter size), as these may influence dosimetric planning and treatment. METHODS: This was a retrospective review using case records of patients who received (90)Y-radioembolization for hepatic tumors at a single tertiary center. From August 2013 to September 2015, seventy-seven out of one hundred and fifty patients who received radioembolization with (90)Y resin microspheres due to inoperable Hepatocellular Carcinoma (HCC) or liver metastases were included. The rest were mainly excluded due to incomplete data sets. The number of split activities (injections) for the radioembolization could be: one single injection, two or three. The remnant activity in post-treatment v-vials and tubing were measured for every patient. The administration arteries evaluated were: proper hepatic artery (PHA), right hepatic artery (RHA), middle hepatic artery (MHA), left hepatic artery (LHA) and small caliber branch arteries. The sizes of the microcatheters (2.2 or 2.7 Fr) used to administer the dose were also evaluated. RESULTS: In total, 77 out of 150 patients were included in the final analysis. There were 59 men of median age 64.0 years old. The total median dose loss was 0.10 GBq. The total dose loss increased 0.244 GBq [95 % CI = (0.169, 0.318)] when three split activities were given compared to single activity injection. Activity loss for each injection increased 0.0297 GBq [95 % CI = (0.0151, 0.0443)] for every 1.0 GBq increase of split activity injection. There were no significant statistical differences in the rest of patient characteristics. CONCLUSIONS: There is significant loss of activity observed during radioembolization, which can have a major dosimetric impact. The total administered activity and the number of split injections during radioembolization are the main influencing factors. Further prospective studies as well as measures of clinical outcome are warranted.

Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities.

INTRODUCTION: Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy. METHODS: The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620-830 µm), which were reduced to 20-40 µm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 10(12) n.cm(-2).s(-1) neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g(-1). Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. RESULTS: Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. CONCLUSION: The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization.