Dataset Information

Yttrium-90 Portal Vein Radioembolization in Sprague-Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver.

ABSTRACT:

Purpose

Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass ⁹⁰Y microspheres (Y90 PVE) in Sprague-Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy.

Methods

Twenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8 MBq; n = 2), high- (99.9 MBq; n = 10), medium- (48.1 MBq; n = 5), and low-dose (14.8 MBq; n = 5). An untreated control group included seven rats. ⁹⁰Y PET/CT of ⁹⁰Y distributions confirmed lobar targeting. MRI volumes were measured at baseline, 2-, 4-, 8- and 12-weeks. Explanted hepatic lobes were weighed, sectioned, and stained for H&E and immunohistochemistry. Digitized slides allowed quantitative measurements of fibrosis (20 foci/slide).

Results

Ex vivo measurements confirmed 91-97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was - 5.0% (95% CI - 17.0-6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6-29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2 μm² for very high- (n = 1), high- (n = 4), medium- (n = 3), and low-dose groups (n = 5), respectively.

Conclusion

Y90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12 weeks. The onset of imaging-based volumetric changes was 8-12 weeks.

SUBMITTER: Gordon AC

PROVIDER: S-EPMC7655630 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundYttrium-90 (90Y) positron emission tomography with integrated computed tomography (PET/CT) represents a technological leap from 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) by coincidence imaging of low abundance internal pair production. Encouraged by favorable early experiences, we implemented post-radioembolization 90Y PET/CT as an adjunct to 90Y bremsstrahlung SPECT/CT in diagnostic reporting.MethodsThis is a retrospective review of all paired 90Y PET/CT and 90Y bremsstrahlung SPECT/CT scans over a 1-year period. We compared image resolution, ability to confirm technical success, detection of non-target activity, and providing conclusive information about 90Y activity within targeted tumor vascular thrombosis. 90Y resin microspheres were used. 90Y PET/CT was performed on a conventional time-of-flight lutetium-yttrium-oxyorthosilicate scanner with minor modifications to acquisition and reconstruction parameters. Specific findings on 90Y PET/CT were corroborated by 90Y bremsstrahlung SPECT/CT, 99mTc macroaggregated albumin SPECT/CT, follow-up diagnostic imaging or review of clinical records.ResultsDiagnostic reporting recommendations were developed from our collective experience across 44 paired scans. Emphasis on the continuity of care improved overall diagnostic accuracy and reporting confidence of the operator. With proper technique, the presence of background noise did not pose a problem for diagnostic reporting. A counter-intuitive but effective technique of detecting non-target activity is proposed, based on the pattern of activity and its relation to underlying anatomy, instead of its visual intensity. In a sub-analysis of 23 patients with a median follow-up of 5.4 months, 90Y PET/CT consistently outperformed 90Y bremsstrahlung SPECT/CT in all aspects of qualitative analysis, including assessment for non-target activity and tumor vascular thrombosis. Parts of viscera closely adjacent to the liver remain challenging for non-target activity detection, compounded by a tendency for mis-registration.ConclusionsAdherence to proper diagnostic reporting technique and emphasis on continuity of care are vital to the clinical utility of post-radioembolization 90Y PET/CT. 90Y PET/CT is superior to 90Y bremsstrahlung SPECT/CT for the assessment of target and non-target activity.

Project description:BackgroundCoincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry.MethodsRetrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET.ResultsPhantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%).ConclusionsTumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

Project description:Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.

Project description:PurposeYttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose.Methods and materialsClinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with >3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical response was defined by Modified Response Evaluation Criteria in Solid Tumours and toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0.ResultsFifty-three patients with HCC and 15 patients with CC/cHCC-CC were analyzed. The median dose delivered was 205 Gy (interquartile range, 183-253 Gy) and 198 Gy (interquartile range, 154-234 Gy) for patients with HCC and CC/cHCC-CC, respectively. The 1-year freedom from local progression rate was 54% (95% confidence interval [CI], 38%-78%) for patients with HCC and 66% (95% CI, 42%-100%) for patients with CC/cHCC-CC. For patients with HCC, United Network for Organ Sharing nodal stage 1 (P = .01), nonsolitary tumors (P = .02), pretreatment α-fetoprotein of >7.7 ng/mL (P = .006), and ≤268 Gy dose delivered (P = .003) were predictors for local progression on multivariate Cox analysis. No patients with HCC who received a dose >268 Gy had a local tumor progression. The 1-year overall survival for patients with HCC was 74% (95% CI, 61%-89%). After radioembolization, 5 (7%) patients had grade 3 ascites, and 4 (6%) patients had grade 3/4 hyperbilirubinemia.ConclusionsTreatment of unresectable primary liver tumors with 90Y radioembolization with an escalated dose was safe and well tolerated. Delivery of >268 Gy may improve local tumor control of HCC. Determination of the maximum tolerated dose needs to be performed in the context of future prospective dose-escalation trials to further evaluate the safety and efficacy of such an approach.