Biokinetic and dosimetric studies of 188Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

Meléndez‐Alafort, Laura; Nadali, Anna; Zangoni, Elena; Banzato, Alessandra; Rondina, Maria; Rosato, Antonio; Mazzi, Ulderico

doi:10.1016/j.nucmedbio.2009.04.006

Cited by 19 publications

(10 citation statements)

References 27 publications

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“…The successful radiolabeling of 99m Tc was found to provide an opportunity for radionuclide 188 Re to be used as internal radionuclide therapy. 48,49 To optimize the 99m Tc labeling, varied activity of 99m Tc was radiolabeled with a fixed HA-CHEMS-Cur-TPGS NPs concentration. The radiolabeling efficiency was similar when varying the activity of 99m Tc from 0.1 mCi to 1 mCi, which meant that we could radiolabel enough 99m Tc for clinical application ( Figure 3E).…”

Section: Resultsmentioning

confidence: 99%

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation

Huang¹,

Chen²,

Zhang³

et al. 2020

IJN

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Background: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)loaded nanoparticle of 99m Tc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics. Materials and Methods: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice. Results: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/ mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99m Tc. The SPECT images showed that 99m Tc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs. Conclusion: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99m Tc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.

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Section: Resultsmentioning

confidence: 99%

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation

Huang¹,

Chen²,

Zhang³

et al. 2020

IJN

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“…Liver sinusoidal endothelial cells were shown to be involved in the clearance of HA-conjugated quantum dots . Liver and spleen are more involved in the clearance of free HA compared to other organs. , The fast clearance and high RES uptake of 175–350 kDa HA-liposomes could potentially be due to their high affinity for other HA receptors such as HARE and LYVE-1, which are abundantly expressed in normal sinusoidal endothelial cells of the liver, spleen, and activated tissue macrophages. , …”

Section: Resultsmentioning

confidence: 99%

Hyaluronan Polymer Length, Grafting Density, and Surface Poly(ethylene glycol) Coating Influence in Vivo Circulation and Tumor Targeting of Hyaluronan-Grafted Liposomes

et al. 2014

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Hyaluronan-grafted liposomes (HA-liposomes) preferentially target CD44-overexpressing tumor cells in vitro via receptor-mediated endocytosis. We investigated the pharmacokinetics and biodistribution of HA-liposomes with various sizes of HA (MW 5–8, 50–60, and 175–350 kDa) in mice. Incorporation of negatively charged HA on the liposome surface compromised its blood circulation time, which led to decreased tumor accumulation in CD44+ human breast cancer MDA-MB-231 xenografts compared to PEGylated liposomes (PEG-5000). Clearance of HA-liposomes was HA polymer length-dependent; high MW (175–350 kDa, highest ligand binding affinity) HA-liposomes displayed faster clearance compared to low MW (5–8, 50–60 kDa) HA-liposomes or PEGylated liposomes. Surface HA ligand density can also affect clearance of HA-liposomes. Thus, HA is not an effective stealth coating material. When dual coating of PEG and HA was used, the PEG-HA-liposomes displayed similar blood circulation time and tumor accumulation to that of the PEGylated liposomes; however, the PEG-HA-liposomes displayed better cellular internalization capability in vivo. Tumor histology showed that PEG-HA-liposomes had a more direct association with CD44+ cancer cells, while PEGylated liposomes located predominantly in the tumor periphery, with less association with CD44+ cells. Flow cytometry analysis of ex vivo tumor cells showed that PEG-HA-liposomes had significantly higher tumor cell internalization compared to PEGylated liposomes. This study demonstrates that a long blood circulation time is critical for active tumor targeting. Furthermore, the use of the tumor-targeting ligand HA does not increase total tumor accumulation of actively targeted liposomes in solid tumors; however, it can enhance intracellular delivery.

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“…Measurement of serum HA level has been used as a marker for evaluating liver damage in people with various liver diseases and in patients who receive physically invasive treatments. Serum HA or its protein complex was increased in cancer patients with HCC or other malignancies [29,30]. The mechanism for the relationship between HA and tumor progression has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Serum Hyaluronic Acid Level and Patient Prognosis in Hepatocellular Carcinoma Patients Who Underwent Hepatectomy

Nanashima¹,

Abo²,

Murakami³

et al. 2013

JCT

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We examined the relationship between hyaluronic acid (HA) and tumor-related factors after hepatectomy in 158 patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. We examined serum HA levels before hepatectomy by evaluating data for clinicopathological parameters, surgical records, postoperative complications and survival. The mean HA level was 190 ± 202 ng/ml. Patients were divided into 3 groups: group A had serum HA levels less than 50 ng/ml (normal range), group B had levels between 50 and 190 ng/ml, and group C had levels over 190 ng/ml. Group C had a higher rate of poor liver function compared to others. Multiple tumors were significantly more frequent in groups B and C compared to A. The grade of fibrosis and the inflammatory responses were positively correlated with the serum HA level. Postoperative long-term ascites was significantly more frequent in group C compared to others. Although the recurrence rate and the relapse-free period were not significantly related to the serum HA level, the serum HA level was significantly associated with overall survival after hepatectomy (p < 0.05). Cox's multivariate analysis did not show a significant relationship between HA level and survival. Serum HA reflects progression and survival in HCC patients.

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Biokinetic and dosimetric studies of 188Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

Cited by 19 publications

References 27 publications

<p><sup>99m</sup>Tc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

<p><sup>99m</sup>Tc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

Hyaluronan Polymer Length, Grafting Density, and Surface Poly(ethylene glycol) Coating Influence in Vivo Circulation and Tumor Targeting of Hyaluronan-Grafted Liposomes

Relationship between Serum Hyaluronic Acid Level and Patient Prognosis in Hepatocellular Carcinoma Patients Who Underwent Hepatectomy

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