90 Y SPECT/CT quantitative study and comparison of uptake with pretreatment 99 m Tc-MAA SPECT/CT in radiomicrosphere therapy.

INTRODUCTION: Yttrium-90 (90 Y) microsphere post-treatment imaging reflects the true distribution characteristics of microspheres in the tumor and liver compartments. However, due to its decay spectra profile lacking a pronounced photopeak, the bremsstrahlung imaging for 90 Y has inherent limitations. The absorbed dose calculations for 90 Y microspheres radiomicrosphere therapy (RMT) sustain a limitation due to the poor quality of 90 Y imaging. The aim of this study was to develop quantitative methods to improve the post-treatment 90 Y bremsstrahlung single photon emission tomography (SPECT)/computed tomography (CT) image analysis for dosimetric purposes and to perform a quantitative comparison with the 99m Tc-MAA SPECT/CT images, which is used for theranostics purposes for liver and tumor dosimetry. METHODS: Pre and post-treatment SPECT/CT data of patients who underwent RMT for primary or metastatic liver cancer were acquired. A Jasczak phantom with eight spherical inserts of various sizes was used to obtain optimal iteration number for the contrast recovery algorithm for improving 90 Y bremsstrahlung SPECT/CT images. Comparison of uptake on 99m Tc-MAA and 90 Y microsphere SPECT/CT images was assessed using tumor to healthy liver ratios (TLRs). The voxel dosimetry technique was used to estimate absorbed doses. Absorbed doses within the tumor and healthy part of the liver were also investigated for correlation with administered activity. RESULTS: Improvement in CNR and contrast recovery coefficients on patient and phantom 90 Y bremsstrahlung SPECT/CT images respectively were achieved. The 99m Tc-MAA and 90 Y microspheres SPECT/CT images showed significant uptake correlation (r = 0.9, P = 0.05) with mean TLR of 9.4 ± 9.2 and 5.0 ± 2.2, respectively. The correlation between the administered activity and tumor absorbed dose was weak (r = 0.5, P > 0.05), however, healthy liver absorbed dose increased with administered activity (r = 0.8, P = 0.0). CONCLUSIONS: This study demonstrated correlation in mean TLR between 99m Tc-MAA and 90 Y microsphere SPECT/CT.

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma.

PURPOSE: This study aimed at identifying prior therapy dosimetric parameters using 99mTc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with 90Y-loaded glass microspheres. METHODS: The dosimetry data of 73 HCC patients were collected prior to the treatment with 90Y-loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated. RESULTS: Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the 90Y-microspheres injection  (r = -0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm3 in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm3 (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%. CONCLUSION: This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results.

High impact of macroaggregated albumin-based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with 90 Y-loaded glass microsphere radioembolization.

BACKGROUND & AIMS: Efficacy of radioembolization is derived from radioinduced damage, whereas tumour dosimetry is not considered as yet in prospective clinical trials. OBJECTIVES: This study evaluates the impact of tumour dose (TD), based on 99m Tc macroaggregated albumin (MAA) quantification, on response and overall survival (OS). MATERIALS AND METHODS: We consecutively included 85 patients with hepatocellular carcinoma treated with 90 Y-loaded glass microspheres. TD was calculated using a quantitative analysis of the MAA SPECT/CT. Responses were assessed after 3 months using the European Association for the Study of the Liver criteria. OS was assessed using Kaplan-Meier tests. RESULTS: Response rate was 80.3% on lesion-based analysis (n=132), and 77.5% on patient-based analysis. The response rate was only 9.1% for patients with TD <205 Gy against 89.7% for those with TD ≥205 Gy (P<10-7 ). Non-portal vein thrombosis (PVT) patients exhibited a median OS of 11.75 m (95% CI: 3-30.7 m) for TD <205 Gy, and 25 m (95% CI: 15-34.7 m) for TD ≥205 Gy (P=.0391). PVT patients exhibited a 4.35 m median OS (95% CI: 2-8 m) for TD<205 Gy, and 15.7 m (95% CI: 9.5-25.5 m) for TD ≥205 Gy, (P=.0004), with HR of 6.99. PVT patients exhibited a median OS of 3.6 m (95% CI: 2-8 m) when PVT MAA targeting was poor or with TD <205 Gy (poor candidate), vs 17.5 m (95% CI: 11-26.5 m) for the others identified as good candidates (P<.0001), with HR of 12.85. CONCLUSION: This study confirms the highly predictive value of MAA-based TD evaluation for response and OS. TD evaluation and PVT MAA targeting should be further evaluated in ongoing trials, whereas personalized dosimetry should be implemented in new trial designs.

A novel tool for motion-related dose inaccuracies reduction in 99mTc-MAA SPECT/CT images for SIRT planning.

INTRODUCTION: In Selective Internal Radiation Therapy (SIRT), 90Y is administered to primary/secondary hepatic lesions. An accurate pre-treatment planning using 99mTc-MAA SPECT/CT allows the assessment of its feasibility and of the activity to be injected. Unfortunately, SPECT/CT suffers from patient-specific respiratory motion which causes artifacts and absorbed dose inaccuracies. In this study, a data-driven solution was developed to correct the respiratory motion. METHODS: The tool realigns the barycenter of SPECT projection images and shifts them to obtain a fine registration with the attenuation map. The tool was validated using a modified dynamic phantom with several breathing patterns. We compared the absorbed dose distributions derived from uncorrected(Dm)/corrected(Dc) images with static ones(Ds) in terms of γ-passing rates, 210 Gy isodose volumes, dose-volume histograms and percentage differences of mean doses (i.e., ΔD¯m and ΔD¯c, respectively). The tool was applied to twelve SIRT patients and the Bland-Altman analysis was performed on mean doses. RESULTS: In the phantom study, the agreement between Dc and Ds was higher (γ-passing rates generally > 90%) than Dm and Ds. The isodose volumes in Dc were closer than Dm to Ds, with differences up to 10% and 30% respectively. A reduction from a median ΔD¯m = -19.3% to ΔD¯c = -0.9%, from ΔD¯m = -42.8% to ΔD¯c = -7.0% and from ΔD¯m = 1586% to ΔD¯c = 47.2% was observed in liver-, tumor- and lungs-like structures. The Bland-Altman analysis on patients showed variations (±50 Gy) and (±4 Gy) between D¯c and D¯m of tumor and lungs, respectively. CONCLUSION: The proposed tool allowed the correction of 99mTc-MAA SPECT/CT images, improving the accuracy of the absorbed dose distribution.

99mTc-MAA/ 90Y-Bremsstrahlung SPECT/CT after simultaneous Tc-MAA/90Y-microsphere injection for immediate treatment monitoring and further therapy planning for radioembolization.

PURPOSE: An angiographic evaluation combined with (99m)Tc-macroaggregated albumin (Tc-MAA) scanning should precede the treatment of any selected candidates for radioembolization (RE) of the liver. If the tumours in one liver lobe have not been targeted in the test angiogram, it should be repeated. However, in a few cases treatment of one liver lobe or at least some segments is safe and feasible and performing a repeated test angiogram with Tc-MAA (Re-MAA) in a separate session leads to more radiation exposure and could be time consuming. Our aim was to evaluate the feasibility of concurrent RE of a part of the liver and therapy planning for another region by simultaneous injection of the Tc-MAA and (90)Y-microspheres in two different locations in the therapy session. Tc-MAA and bremsstrahlung (BS) single photon emission computed tomography (SPECT)/CT were performed separately in an effort to distinguish between the distributions of these two different radiopharmaceuticals. METHODS: RE was combined with a simultaneous second test angiogram of another lobe or segments in the same session in six patients [44-70 years; five women (83%)]. Five patients suffered from colorectal carcinoma (CRC) and one from ovarian cancer. Tc-MAA and BS SPECT/CT were performed for all cases. RESULTS: Post-therapeutic Tc-MAA SPECT/CT showed in all patients only the distribution of Tc-MAA without any detectable BS. Evaluation of (90)Y-microsphere distribution was not always possible in the post-therapeutic BS scan performed 24 h later due to remaining Tc-MAA radiation. However, scans performed at 48 h post-intervention no longer showed any Tc-MAA "contamination". CONCLUSION: Combining RE and Re-MAA is feasible in appropriately selected patients.

Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization.

PURPOSE: To assess the feasibility of performing same-day vascular flow redistribution and Yttrium-90 radioembolization (90Y-RE) for hepatic malignancies. MATERIALS AND METHODS: From November 2015 to February 2019, patients undergoing same-day hepatic flow redistribution during work-up angiography, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) SPECT/CT and 90Y microsphere-RE, were recruited. Within 18 h following the delivery of 90Y resin microspheres, an 90Y-PET/CT study was performed. According to patients' vascular anatomy, flow redistribution was performed by microcoil embolization of extrahepatic branches (group A), intrahepatic non-tumoral vessels (group B) and intrahepatic tumoral arteries (group C). The accumulation of 99mTc-MAA particles and microspheres in the redistributed areas was qualitatively evaluated using a 5-point visual scale (grade 1 = < 25% accumulation; grade 5 = 100% accumulation). Differences in the distribution of microspheres among groups were assessed with Mann-Whitney U test. RESULTS: Twenty-two patients were treated for primary (n = 17) and secondary (n = 5) hepatic malignancies. The MAA-SPECT/CT showed uptake in all the redistributed areas. Regarding the accumulation of microspheres within the redistributed segments in all the groups, perfusion patterns were classified as 2 in 1 case, 4 in 6 cases and 5 in 15 cases. No statistically significant differences were observed between groups A and B-C (U value = 34, p = 0.32) and between groups B and C (U value = 26, p = 0.7). Mean predicted absorbed doses by the tumoral and normal hepatic tissues were 163.5 ± 131.2 Gy and 60.4 ± 69.3 Gy, respectively. Mean total procedure time (from work-up angiography to 90Y delivery) was 401 ± 0.055 min. CONCLUSION: Performing same-day redistribution of the arterial hepatic flow to the target and 90Y-microsphere delivery is feasible in the treatment of liver tumors. Clinical Trials Registry NCT03380130.

Hepatic selective internal radiation therapy: how well does pretreatment 99mTc-macroaggregated albumin activity distribution and quantification agree with post-therapy bremsstrahlung imaging?

AIM: The aim of this study was to examine the agreement of pretreatment Tc-macroaggregated albumin imaging performed for selective internal radiation therapy (SIRT) workup with Y percentage lung shunt (PLS) and regional hepatic distribution in subsequent post-therapy bremsstrahlung imaging. PATIENTS AND METHODS: Planar images were used to calculate PLS. The significant Y bremsstrahlung scatter required background correction. Results using both Y lung background regions of interest (ROI) reported in previous studies and extended ROIs (reflecting lung background variation) were compared with Tc-MAA PLS. Lesion and healthy liver volumes were outlined on diagnostic computed tomography scans and registered to Tc-MAA and Y single-photon emission computed tomography/computed tomographydata. Single-photon emission computed tomography voxel values were normalized to injected Y activity. Volume mean activities were calculated, and converted into the mean absorbed dose. Agreement was quantified using Bland-Altman analysis. RESULTS: PLS: The bias using previous studies' lung background ROIs was -10.71%, with a 95% confidence interval (CI) of -18.79 to -2.64%. The extended ROI yielded a bias of 0.77% (95% CI: -2.23 to 3.70%). Liver: The healthy liver bias was 0.01 MBq/ml (0.17 Gy), with a -0.05 to 0.06 MBq/ml (95% CI:0.80 -1.93 Gy). The lesion mean activity/ml bias was -0.02 MBq/ml (3.71 Gy), with a -0.81 to 0.76 MBq/ml (95% CI: -35.49 to 28.07 Gy). CONCLUSIONS: The PLS agreement was sensitive to the Y lung background correction ROI, potentially explaining a previously published controversy. The mean activity and absorbed dose agreement for the metastatic lesions was poorer than the healthy liver volumes studied here.

Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for Hepatocellular Carcinoma Patients Treated With Radioembolization.

OBJECTIVE: As the utility of Child-Pugh (C-P) class is limited by the subjectivity of ascites and encephalopathy, we evaluated a previously established objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for yttrium-90 radioembolization (RE) treatment for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 117 patients who received RE for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS) according to these 3 criteria was evaluated by Kaplan-Meier survival analysis. The utilities of C-P class and ALBI grade as prognostic indicators were compared using the log-rank test. Multivariate Cox regression analysis was performed to identify additional predictive factors. RESULTS: Patients with ALBI grade 1 (n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile, no significant difference was observed in OS between C-P class A (n=100) and C-P class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was able to stratify 2 clear and nonoverlapping subgroups with differing OS curves (P=0.03). Multivariate Cox regression test identified alanine transaminase, Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic factors for OS (P<0.10). CONCLUSIONS: ALBI grade as a prognosticator has demonstrated clear survival discrimination that is superior to C-P class among HCC patients treated with RE, particularly within the subgroup of C-P class A patients. ALBI grade is useful for clinicians to make decisions as to whether RE should be recommended to patients with HCC.

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.

The Caudate Lobe: The Blind Spot in Radioembolization or an Overlooked Opportunity?

PURPOSE: The caudate lobe (CL) is impartial to the functional left and right hemi-liver and has outspoken inter-individual differences in arterial vascularization. Unfortunately, this complexity is not specifically taken into account during radioembolization treatment (RE), potentially resulting in under- or overtreatment of the CL. The objective of this study was to evaluate the CL coverage in RE and determine the detection rate of the CL arteries on CT angiography during work-up. METHODS: In all consecutive patients who underwent RE treatment between May 2012-January 2015, (99m)Tc-MAA SPECT/CT and posttreatment scans ((90)Y-bremsstrahlung SPECT/CT, (90)Y-PET/CT, or (166)Ho-SPECT/CT) were reviewed for activity in the CL. Pretreatment CT angiographies were reviewed for the visibility of the CL arteries. RESULTS: Eighty-two patients were treated. In 32/82 (39 %) the CL was involved. In 6/32 (19 %) patients, no activity was seen on the posttreatment scan in the CL, whereas in 40/50 (80 %) patients without CL tumor involvement, the CL was treated. (99m)Tc-MAA SPECT/CT and final posttreatment scans were discordant in 16/78 (21 %). (99m)Tc-MAA SPECT/CT had a positive and negative predictive value of 94 % and 46 %, respectively, for activity in the CL after RE. In untreated CLs, significant hypertrophy was observed with a median volume increase of 33 % (p = 0.02). CL arteries were seldom visible on the pretreatment CT; the identification rate was 12-17 %. CONCLUSION: Currently in RE treatments, targeting or sparing of the CL is highly erratic and independent of tumor involvement. Intentional treatment or bypassing of the CL seems worthwhile to either improve tumor coverage or enhance the functional liver remnant.

Increased capillary permeability to albumin and diabetic neuropathy.

An increase in the capillary permeability to albumin (CPA) has been reported in diabetic patients. We observed this frequently with a non-invasive isotopic test derived from the Landis method, using 99mTc-albumin and measuring residual radioactivity externally after removal of forearm venous compression. Evidence of the independent effects of hypertension and microangiopathy on CPA has already been found. The present work was designed to investigate CPA using the same test on diabetic patients without retinopathy and clinical proteinuria. Some of these patients had objective clinical distal and symmetrical polyneuropathy. Neuropathy was clearly present in 10 of the 11 patients with an abnormal test unexplained by causes other than diabetes and in only one of the 17 patients with a normal test. The most frequent abnormality affected the late radioactivity disappearance curve, which probably reflects an impaired lymphatic wash-out of interstitial albumin. These results strongly suggest a link between peripheral neuropathy and diabetic functional microangiopathy. An elevated blood flow secondary to sympathetic nerve failure may induce an increase in CPA and a saturation of lymphatic pumping which could also be deficient due to impaired lymphatic innervation.

Radioguided-surgery of early breast lesions.

BACKGROUND: Radioguided-surgery has been recently proposed in patients with clinically occult breast lesions. This study aimed to evaluate the feasibility of correctly locating and eradicating, by a single intralesional injection of a radiotracer, any breast lesion and, in the case of malignancy, to perform simultaneous sentinel lymph node (SLN) biopsy procedure. PATIENTS AND METHODS: Sixty-three women with early breast lesions were enrolled: 42 were invasive carcinomas, 16 in situ ductal carcinomas (DCIS) and 5 fibroadenomas. RESULTS: Scintigraphic images clearly identified the lesions in all patients while SLN/s were evident in 88% of them. At surgery all the breast lesions were easily radiolocalized and eradicated with minimum surgical trauma and, for those patients with invasive carcinomas, the SLN technique was performed in 86% of them. No skip metastases were found. CONCLUSION: A single intralesional administration of radiotracer is an easy and reliable procedure to simultaneously locate and remove both the non-palpable breast lesion and the SLN when primary malignancy was intraoperatively confirmed.

Evaluation of the ventilation-perfusion ratio in lung diseases by simultaneous anterior and posterior image acquisition.

Ventilation and perfusion images were acquired during tidal breathing using 81mKr gas and 99mTc-MAA. Anterior and posterior functional images of V/Q and Q/V were simultaneously acquired in 34 subjects with various lung diseases and 6 healthy controls. Superimposed anterior and posterior images were constructed and histograms of the frequency distribution for ventilation, perfusion, and the V/Q ratio were displayed for both lungs as well as for the left and right lungs individually. Blood gas analysis and general lung function tests were also performed on the day before scintigraphy. A correlation between marked uneven distribution of V/Q and A-aDO2 was found. When the proportion of counts at V/Q < 0.67 and/or V/Q > 1.50 in the V/Q counts histogram was compared with A-aDO2, there was a significant positive correlation for anterior images (r = 0.684, p < 0.05), posterior images (r = 0.654, p < 0.05) and superimposed images (r = 0.696, p < 0.05). Superimposed images therefore showed the highest correlation. There was no correlation between the results of lung function testing and A-aDO2. Coronal SPECT images were also obtained in 15 patients and compared with the superimposed anterior and posterior planar images. There was a good correlation (r = 0.888, p < 0.001) between both the imaging methods regarding the marked uneven distribution of V/Q. Simultaneous anterior and posterior planar image acquisition reduces the examining time, is simple, and is noninvasive. The present results also suggest that it is useful for quantitative evaluation of the ventilation-perfusion ratio.

Selective internal radiotherapy (SIRT) of hepatic tumors: how to deal with the cystic artery.

PURPOSE: Selective internal radiotherapy (SIRT) with the beta emitter yttrium-90 (Y90) is a rapidly developing therapy option for unresectable liver malignancies. Nontarget irradiation of the gallbladder is a complication of SIRT. Thus, we aimed to assess different strategies to avoid infusion of Y90 into the cystic artery (CA). METHODS: After hepatic digital subtraction angiography and administration of technetium-99m-labeled human serum albumin ((99)mTc-HSA), 295 patients with primary or secondary liver tumors underwent single-photon emission computed tomography/computed tomography (SPECT/CT). Different measures were taken before repeated Y90 mapping and SIRT to avoid unintended influx into the CA where necessary. Clinical symptoms, including pain, fever, or a positive Murphy sign, were assessed during patient follow-up. RESULTS: A significant (99)mTc-HSA accumulation in the gallbladder wall (higher (99)mTc-HSA uptake than in normal liver tissue) was seen in 20 patients. The following measures were taken to avoid unintended influx into the CA: temporary/permanent occlusion of the CA with gelfoam (n = 5)/microcoil (n = 1), induction of vasospasm with a microwire (n = 4), or altering catheter position (n = 10). Clinical signs of cholecystitis were observed in only one patient after temporary CA occlusion with gelfoam and were successfully treated by antibiotics. Cholecystectomy was not required for any patient. CONCLUSION: It is important to identify possible nontarget irradiation of the gallbladder. The risk for radiation-induced cholecystitis can be easily minimized by temporary or permanent CA embolization, vasospasm induction, or altering the catheter position.

Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial.

BACKGROUND: Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases. METHODS: The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. DISCUSSION: This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.

Safety and efficacy assessment of flow redistribution by occlusion of intrahepatic vessels prior to radioembolization in the treatment of liver tumors.

We evaluated the feasibility, safety, and efficacy of radioembolization (administered from one or two vascular points) after the redistribution of arterial blood flow in the liver in patients with hepatic neoplasms and arterial anatomic peculiarities (AAP). Twenty-four patients with liver neoplasms and AAP (graded according to Michel's classification) were included in the study. During pretreatment angiographic planning, all extrahepatic vessels that could feed the tumor were embolized and the intrahepatic vessels occluded in order to redistribute blood flow. The distribution of microspheres was initially assessed by using technetium-99m-labeled macroaggregated albumin ((99m)Tc-MAA) from one of two vascular points before the administration of yttrium-90 ((90)Y)-radiolabeled resin microspheres. Perfusion of lesions situated in the redistributed segments (L-RS) and nonredistributed segments (L-NRS) were compared by assessing the distribution of (99m)Tc-MAA by SPECT/CT. Perfusion was graded as normal, reduced, or absent. (90)Y resin microspheres were then injected from the same arterial sites as (99m)Tc-MAA and the tumor response recorded 3 months later. The tumor response in L-RS was compared with that in L-NRS and graded as better, similar, or worse. Among 11 patients with type I AAP in whom mainly vessels in segments I-III or IV were occluded, perfusion of L-RS was graded as similar (n = 7) or reduced (n = 4). Among the remaining 13 patients with AAP types III (n = 3), V (n = 4), VIII (n = 3), and others (n = 3) in which aberrant arteries were occluded, perfusion of L-RS was graded as similar (n = 9), reduced (n = 3), or absent (n = 1). Overall, (99m)Tc-MAA was present in the L-RS of 95.8% patients and the distribution of (99m)Tc-MAA in L-RS and L-NRS were graded as similar in 66.6% of patients. Compared with lesions in the L-NRS, tumor response in L-RS was similar in 23 cases and worse in 1 case. No complications were recorded after the administration of (90)Y resin microspheres. Redistribution of flow in L-RS is feasible and enables a safe and effective delivery of (90)Y resin microspheres that are able to be distributed via intrahepatic collaterals and access the microvasculature of L-RS.

Effect of voxel size and computation method on Tc-99m MAA SPECT/CT-based dose estimation for Y-90 microsphere therapy.

The use of selective internal radiation therapy for treatment of hepatocellular carcinoma and liver metastases using Y-90 labeled microspheres has become an effective and widely used treatment regimen. However, dosimetric evaluations of this treatment are still primitive as uniform distribution models based only on injected activity are often used. This investigation attempts to quantify the effectiveness of several sophisticated patient-specific techniques which utilize the source distribution of Tc-99m MAA simulation studies to perform voxelized dosimetric computations. Among these techniques are complete Monte-Carlo radiation transport computation in patient-specific CT-based voxel phantoms, local energy deposition in patient specific phantoms and kernel transport techniques in water. Each technique was evaluated using three different phantom voxel dimensions and SPECT reconstruction matrix sizes. Dose evaluation results using all methods were compared to the exact solution, obtained using fully 3-D Monte-Carlo simulations with source distribution based not on SPECT data, but on the injected activity and exact boundaries of the anthropomorphic phantom used in the study. The results of this study show that at large voxel sizes and using SPECT reconstructions with a small matrix size (64 x 64), Monte-Carlo and local deposition methods are nearly equivalent. However, using a large SPECT reconstruction matrix (256 x 256) the local deposition method is significantly more accurate than full 3-D Monte-Carlo transport, and with a negligible computational burden.