Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model

Wu, Yu-Hsien; Liu, I-Hshiang; Ho, Chung-Li; Lee, Wan-Chi; Chang, Cheng-Yen; Lan, Keng‐Li; Ting, Gann; Lee, Te‐Wei; Shien, Jui-Hung

doi:10.1016/j.nucmedbio.2011.06.010

Cited by 35 publications

(32 citation statements)

References 26 publications

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“…This phenomenon may cause potent side effects (15,22,27). Indeed, our biodistribution study revealed that accumulation of 188 Re-liposome in the liver and spleen could remain up to 48 h, but 188 Re-BMEDA washed out after 24 h of administration.…”

Section: Discussionmentioning

confidence: 85%

“…It has been reported that the administration of 188 Re in murine colorectal cancer and human prostate cancer models could lead to significant tumor-killing effects and extend the survival of the animals through the emitted b particles (11,15,31). Although we have demonstrated that the life span of tumor-bearing mice was extended by PEGylated 188 Re-liposome, the BLI data showed that the orthotopic lung tumors were not eradicated but their growth was suppressed.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, it has been reported that conjugation of 188 Re to monoclonal antibodies and hydroxyethylidene diphosphonate can suppress cancer growth and relieve the pain caused by bone metastasis, respectively (12)(13)(14). Recently, 188 Re has been embedded in nanoscale liposomes via N,N-bis(2-mercaptoethyl)-N9,N9-diethylethylenediamine (BMEDA) chelator and proved to be ideal for targeting in the local and lung metastatic colorectal cancer animal model (15). Additionally, conjugation of 188 Re or 99m Tc to the somatostatin receptor-binding peptide analog P2045 has been demonstrated to be a potent radiopharmaceutical for lung cancer therapy and diagnosis, and it has entered phase I clinical trials (16)(17)(18).…”

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confidence: 99%

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Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Lin

Chang

et al. 2014

J Nucl Med

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Non-small cell lung cancer (NSCLC) is a highly morbid and mortal cancer type that is difficult to eradicate using conventional chemotherapy and radiotherapy. Little is known about whether radionuclide-based pharmaceuticals can be used for treating NSCLC. Here we embedded the therapeutic radionuclide 188 Re in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharmacokinetics, and therapeutic efficacy of this nanoradiopharmaceutical on NSCLC using a xenograft lung tumor model and the reporter gene imaging techniques. Methods: Human NSCLC NCI-H292 cells expressing multiple reporter genes were used in this study. 188 Re was conjugated to N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) and loaded into the PEGylated liposome to form a 188 Reliposome. The tumor growth rates and localizations were confirmed using bioluminescent imaging and SPECT/CT after the 188 Re-BMEDA or 188 Re-liposome was intravenously injected. The accumulation of the nanodrug in various organs was determined by the biodistribution analysis and the nano-SPECT/CT system. The pharmacokinetic and dosimetric analyses were further determined using WinNonlin and OLINDA/EXM, respectively. Results: The biodistribution and nano-SPECT/CT imaging showed that PEGylated 188 Re-liposome could efficiently accumulate in xenograft tumors formed by NCI-H292 cells that were subcutaneously implanted in nude mice. Pharmacokinetic analysis also showed that the retention of 188 Re-liposome was longer than that of 188 Re-BMEDA. In an orthotopic tumor model, ex vivo γ counting revealed that the uptake of 188 Re-liposome was detected in tumor lesions but not in surrounding normal lung tissues. Moreover, we evaluated the therapeutic efficacy using bioluminescent imaging and showed that the lung tumor growth was suppressed but not eradicated by 188 Re-liposome. The life span of 188 Re-liposometreated mice was 2-fold longer than that of untreated control mice. Conclusion:The results of biodistribution, pharmacokinetics, estimated dosimetry, nano-SPECT/CT, and bioluminescent imaging suggest that the PEGylated liposome-embedded 188 Re could be used for the treatment of human lung cancers.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Lin

Chang

et al. 2014

J Nucl Med

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“…13 Re-liposome has a comparative therapeutic efficacy with chemotherapeutic drug 5-FU in colon carcinoma ascites, we found that 188 Re-liposome possesses a better therapeutic efficacy in both lung-metastatic and solid-tumor animal models. 18,[20][21][22] No documents using 188…”

Section: Introductionmentioning

confidence: 99%

External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

Chang¹,

Liu²,

Wen³

et al. 2015

IJN

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External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 ( 188 Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of 188 Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188 Re-liposome. The combination of EBRT and 188 Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188 Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188 Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188 Re-liposome might be a potential treatment modality for esophageal cancer.

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“…The imaging protocol was in accordance with that previously described, but with some modifications. 26,27 For in vitro imaging, F98 luc cells were diluted from 100,000 to 195 cells by culture medium and each group of cells (in 100 μL) was carefully loaded into a black 96-well plate. Then, the D -Luciferin substrate (in medium) was added to each well at a concentration of 150 μg/mL for 5 minutes incubation and the cells-loaded plate was imaged continuously for 1 minute with the IVIS™ system.…”

Section: Blimentioning

confidence: 99%

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

Huang

Lee

Chang

et al. 2015

IJN

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Purpose In this study, the 188 Re-labeled PEGylated nanoliposome ( 188 Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98 luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188 Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188 Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188 Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98 luc ) showed a high relationship between cell number and its bioluminescent intensity ( R 2 =0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188 Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188 Re-liposome-treated group than the control group ( P <0.05). As a result, the lifespan of glioma-bearing rats treated with 188 Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188 Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, 188 Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.

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Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model

Cited by 35 publications

References 26 publications

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

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Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model

Cited by 35 publications

References 26 publications

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded 188Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded 188Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer&nbsp;xenograft and modulates 188Re-liposome pharmacokinetics

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

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Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome–Embedded ¹⁸⁸Re on Human Non–Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics