Tumor-specific enhancer/promoter is applicable for targeting gene expression in tumors and helpful for tumortargeting imaging and therapy. We aimed to acquire a-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) specific images using adenovirus containing HSV1-tk gene controlled by AFP enhancer/promoter and evaluate in vivo ganciclovir (GCV)-medicated therapeutic effects on AFP-targeted HSV1-tk expression with 18 F-FDG positron emission tomography (PET). Recombinant adenovirus expressing HSV1-tk under AFP enhancer/promoter was produced (AdAFP-TK) and the expression levels were evaluated by I-IVDU uptake. GCV-mediated HSV1-tk cytotoxicity was determined by MTT assay. After the mixture of AdAFP-fLuc and AdAFP-TK was administrated, bioluminescent images (BLIs) and 18 F-FHBG PET images were obtained in tumor-bearing mice. In vivo therapeutic effects of AdAFP-TK and GCV in the HuH-7 xenograft model were monitored by 18 F-FDG PET. When infected with AdAFP-TK, cell viability in HuH-7 was reduced, but those in HT-29 and SK-Hep-1 were not significantly decreased at any GCV concentration less than 100 lM. AFP-targeted fLuc and HSV1-tk expression were clearly visualized by BLI and 18 F-FHBG PET images in AFP-producing HCC, respectively. In vivo GCV-mediated tumor growth inhibition by AFP-targeted HSV1-tk expression was monitored by 18 F-FDG PET. Recombinant AdAFP-TK could be applied for AFPtargeted HCC gene therapy and imaging in AFP-producing HCC.

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Continuous irradiation with exponentially reducing beta-rays induces cell death, known as apoptosis. The aim of this study was to investigate the G2 arrest and apoptosis caused by the beta-ray emitted by the radioisotope (188)Re. Doses of 0.4 Gy (3.7 MBq), 4 Gy (37 MBq), and 40 Gy (370 MBq), were added to Blymphoma Raji cells, and cell viability, apoptosis, and DNA cell-cycle changes were assayed. (188)Re showed time- and dose-dependent effects on cell viability and on cell apoptosis and necrosis. At a (188)Re dose of 0.4 Gy, G(2) cell-cycle arrest was observed after 16 hours, and 4,6-diamidino-2-phenylindole (DAPI) staining indicated a slow, time-dependent increase in apoptotic bodies. At a (188)Re dose of 40 Gy, DNA fragmentation was observed at 2 hours, indicative of early damage in the nucleus. In summary, our results showed that continuous irradiation with low-dose beta-rays induced G(2) arrest and progressive apoptosis, which may be characteristic mechanisms of radionuclide therapy.

We investigated the off‐target binding of amyloid‐beta (Aβ) target [18F]florapronol ([18F]FC119S) using postmortem Alzheimer's disease (AD) brain tissue, compared with a known Aβ target imaging agent, [125I]TZDM and tau targeting [125I]MK as positive and negative controls, respectively. Off‐target binding of monoamine oxidase‐A and ‐B (MAO‐A and ‐B) was screened for FC119S and Pittsburgh compound B (PiB). Autoradiography (ARG) was performed to screen the Aβ‐binding potential using human AD postmortem brain tissue sections. Colocalization was quantitatively analyzed by using image analysis software. Pathological analysis was performed for screening of specific binding of amyloid‐beta and phospho‐tau. Amyloid‐beta targeting [18F]FC119S and [125I]TZDM tracers were showed a similar binding pattern in ARG, but [125I]MK was showed a different binding patterns. In the blocking experiment, [18F]FC119S binding was effectively blocked by a cold TZDM compound. FC119S and PiB were not showed specific binding with MAO‐A and MAO‐B. The autoradiographic binding pattern was positively correlated with the Aβ expression.

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