Dataset Information

Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma.

ABSTRACT: Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (111In/177Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of 111In/177Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the 111In/177Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of 177Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of 177Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. 111In/177Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma.

SUBMITTER: Chan HW

PROVIDER: S-EPMC8953182 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma.

Chan Hui-Wen HW Lo Yi-Hsuan YH Chang Deng-Yuan DY Li Jia-Je JJ Chang Wen-Yi WY Chen Chih-Hao CH Chang Chih-Hsien CH Chen Chuan-Lin CL Wang Hsin-Ell HE Liu Ren-Shyan RS Wu Chun-Yi CY

Gels (Basel, Switzerland) 20220314 3

Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (111In/177Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of 111In/177Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the 111In/177Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administratio ...[more]

PMID: 35323293

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Project description:INTRODUCTION:Strong correlation has been demonstrated between tumor dose and response and between healthy liver dose and side effects. Individualized dosimetry is increasingly recommended in the current clinical routine. However, hepatic and tumor segmentations could be complex in some cases. The aim of this study is to assess the reproducibility of the tumoral and non-tumoral liver dosimetry in selective internal radiation therapy (SIRT). MATERIAL AND METHODS:Twenty-three patients with hepatocellular carcinoma (HCC) who underwent SIRT with glass microspheres were retrospectively included in the study. Tumor (TV) and total liver volumes (TLV), and mean absorbed doses in tumoral liver (TD) and non-tumoral liver (THLD) were determined on the 90Y PET/CT studies using Simplicit90YTM software, by three independent observers. Dosimetry datasets were obtained by a medical physicist helped by a nuclear medicine (NM) physician with 10 years of experience (A), by a NM physician with 4-year experience (B), and by a resident who first performed 10 dosimetry assessments as a training (C). Inter-observer agreement was evaluated using intra-class correlation coefficients (ICC), coefficients of variation (CV), Bland-Altman plots, and reproducibility coefficient (RDC). RESULTS:A strong agreement was observed between all three readers for estimating TLV (ICC 0.98) and THLD (ICC 0.97). Agreement was lower for TV delineation (ICC 0.94) and particularly for TD (ICC 0.73), especially for the highest values. Regarding TD, the CV (%) was 26.5, 26.9, and 20.2 between observers A and B, A and C, and B and C, respectively, and the RDC was 1.5. Regarding THLD, it was 8.5, 12.7, and 9.4, and the RDC was 1.3. CONCLUSION:Using a standardized methodology, and regardless of the different experiences of the observers, the estimation of THLD is highly reproducible. Although the reproducibility of the assessment of tumor irradiation is overall quite high, large variations may be observed in a limited number of patients.

Project description:A selective intra-arterial liver injection using yttrium-90-loaded microspheres as sources for internal radiation therapy is a form of transarterial radioembolization (TARE). Current data from the literature suggest that TARE is effective in hepatocellular carcinoma (HCC) and is associated with a low rate of adverse events; however, they are all based on retrospective series or non-controlled prospective studies, since randomized controlled trials comparing the other liver-directed therapies for intermediate and locally advanced stages HCC are still ongoing. The available data show that TARE provides similar or even better survival rates. TARE is very well tolerated and has a low rate of complications; these complications do not result from the embolic effects but mainly from the unintended irradiation to non-target tissue, including the liver parenchyma. The complications can be further reduced by accurate patient selection and a strict pre-treatment evaluation, including dosimetry and assessment of the vascular anatomy. First-line TARE is best indicated for intermediate-stage patients (according to the Barcelona Clinic Liver Cancer [BCLC] staging classification) who are poor candidates for transarterial chemoembolization or patients having locally advanced disease with segmental or lobar branch portal vein thrombosis. Moreover, data are emerging regarding the use of TARE in patients classified slightly above the criteria for liver transplantation with the purpose of downstaging them. TARE can also be applied as a second-line treatment in patients progressing to transarterial chemoembolization or sorafenib; a large number of Phase II/III trials are in progress in order to evaluate the best association with systemic therapies. Given the complexity of a correct treatment algorithm for potential TARE candidates and the need for clinical guidance, a comprehensive review was carried out analyzing both the best selection criteria of patients who really benefit from TARE and the new advances of this therapy which add significant value to the therapeutic weaponry against HCC.

Project description:BackgroundCurrently, inoperable hepatocellular carcinoma (HCC) is treated by both transarterial radioembolization (TARE) and transarterial chemoembolization (TACE). However, their relative efficacy and outcomes remain unclear. This meta-analysis aimed to compare TARE and TACE to evaluate their safety and efficacy in treating inoperable HCC patients.MethodsRelevant studies were identified by searching the Web of Science, PubMed, and Wanfang databases. Pooled analyses were used to compare treatment response rates, complications, and overall survival (OS) outcomes between the TARE and TACE groups.ResultsThis analysis selected 8 studies comprising 1026 and 358 patients that respectively underwent TACE and TARE treatment. The results revealed that the TARE group had significantly higher pooled total response, disease control, and 1-year OS rates compared to the TACE group (P = 0.04, 0.003, and 0.02, respectively), with a corresponding increase in OS (P = 0.0002). Furthermore, rates of complications including fever and abdominal pain were also reduced in the TARE group (P = 0.006 and 0.02, respectively). Moreover, there were no significant differences in the pooled analyses of complete response rates, fatigue, nausea/vomiting, 3-year OS, or 5-year OS between these groups (P = 0.24, 0.69, 0.15, 0.73, and 0.38, respectively). Significant heterogeneity was detected for endpoints including fatigue, nausea/vomiting, fever, abdominal pain, OS duration, and 3-year OS (I2 = 89%, 82%, 72%, 90%, 96%, and 66%, respectively). All endpoints exhibited no significant risk of publication bias.ConclusionsThis study revealed that relative to TACE, TARE performed using 90Y can yield significantly higher treatment response rates and prolong HCC patient survival with fewer treatment-related side effects.The PRISMA guidelines were used to guide the execution and publication of this meta-analysis. The study is registered at INPLASY.COM (No. INPLASY202380017).Systematic review registrationINPLASY.COM, identifier INPLASY202380017.

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.

Dataset Information

Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma.

Publications

Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma.

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