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.
Electron spin echo envelope modulations (ESEEM) of photoexcited anthracene in p-terphenyl crystals at room temperature are reported. Sources of contribution to the observed ESEEM have been established. The hyperfine tensor elements of the anthracene triplet have been determined and compared with the results of the previous ENDOR study.excitation source was the third harmonic of a Nd:YAG laser (X = 355 nm) with 30-mJ maximum energy. The FFT program is a Nicolet NMR software package. Electron Spin Echo Envelope Modulations and ENDOR Frequencies Below we shall present only the results of two-pulse (tt/2 -t -) experiments. For a one nucleus (I = 1/2) system,
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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