Yoshihiro Nakagami

Value of 18F-FDG PET in the detection of peritoneal carcinomatosis

PurposePeritoneal carcinomatosis can be difficult to diagnose using computed tomography (CT). The purpose of this study was to evaluate the role of 2-(fluorine 18) fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the detection of peritoneal carcinomatosis.MethodsWe reviewed the CT and FDG PET radiological reports and clinical charts of 18 patients with peritoneal carcinomatosis and 17 cancer patients without peritoneal carcinomatosis. We also assessed FDG PET scans from 20 healthy volunteers as a baseline study. The maximum standardised uptake values (SUVmax) over peritoneal lesions in cancer patients and over the area of most intense intestinal uptake in healthy volunteers and cancer patients without peritoneal carcinomatosis were measured.ResultsThe sensitivity and positive predictive value (PPV) of combined FDG PET and CT were superior to those of CT alone for the detection of peritoneal lesions (sensitivity: 66.7% vs 22.2%, p<0.025; PPV: 92.3% vs 50.0%, p<0.05). The most frequent pattern of FDG uptake in patients with peritoneal carcinomatosis was abnormally intense focal uptake near the abdominal wall. An SUVmax threshold of 5.1 produced a diagnostic accuracy of combined FDG PET and CT of 78%. The additional information provided by FDG PET allowed a more accurate diagnosis in 14 patients (40.0%), and led to alteration of the therapeutic strategy in five (14.3%) of the enrolled cancer patients.ConclusionWe found that use of an intra-abdominal FDG uptake cut-off value for SUVmax of >5.1 assists in the diagnosis of peritoneal carcinomatosis. FDG PET may play an important role in the clinical management of patients with suspected peritoneal carcinomatosis.

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

The objective of the present study was to establish an orthotopic tumor transplantation model in nude mice that closely resembles the clinical features of human lung cancer. The human lung adenocarcinoma A549 cell line and the squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum‐free medium were injected directly into the main bronchi of anesthetized female Balb/c athymic nude mice (7–9 weeks old) with or without simultaneous administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some experiments, lung carcinoma cells harvested from tumors transplanted subcutaneously were recultured and used for intratracheal implantation. Tumor nodules that formed in the lung were counted and confirmed by histological examination. Administration of A549 cells with EDTA resulted in a 70% engraftment rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n = 5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates, respectively. Recultured SQ5 cells with EDTA further increased the engraftment rate to 100% (n = 6). Multiple tumors formed mainly in the left lung and the upper lobe of the right lung. Simultaneous administration of EDTA resulted in greater numbers of tumor nodules in the lung. Histological findings revealed that A549 tumor nodules were distributed primarily in alveoli. The SQ5 solid tumors invaded bronchioles and occupied the alveoli. This reproducible orthotopic transplantation model produced tumor growth that simulated the clinical features of human lung cancer. (Cancer Sci 2006; 97: 996–1001)

Nuclear translocation of DNase II and acid phosphatase during radiation-induced apoptosis in HL60 cells.

DNase II is involved in DNA fragmentation induced by a variety of treatments. However, according to past reports DNase II does not directly generate TUNEL (in situ DNA end labeling)-positive cells. The purpose of this study was to investigate the participation of acid phosphatase in the generation of TUNEL-positive cells. DNase II-like proteins, whose molecular weights were 32-kDa, were detected in nuclear extracts of HL60 human myeloid leukemia cells post γ-irradiation by SDS-PAGE and immunohistochemistry. Acidic nuclease activity was especially active in 32-kDa bands. TUNEL assay was positive post γ-irradiation. From measurements of the activity of acid phosphatase, the activity in nuclear extracts increased remarkably post γ-irradiation. γ-irradiation can directly or indirectly activate DNase II. Once DNase II and acid phosphatase have been translocated from lysosomes into the nuclei, DNase II generates TUNEL reactive ends in combination with acid phosphatase.

A simulation study for estimating scatter fraction in whole-body 18F-FDG PET/CT

AbstractWhereas Monte Carlo (MC) simulation is widely utilized in estimation of the scatter component, a simulation model which can calculate the scatter fraction (SF) of each patient is needed for making an accurate image quality assessment for clinical PET images based on the noise equivalent count. In this study, an MC simulation model was constructed which can calculate the SF for various phantoms. We utilized the Geant4 toolkit based on MC simulation to make a model of a PET scanner with a scatter phantom, and SFs calculated with this model were compared with the SF (SFconstant: 44%) measured with use of an actual PET scanner. Additionally, the SF values for an anthropomorphic phantom were calculated from its voxel phantom. Furthermore, we evaluated the impact on the SF due to the difference in the source distribution inside the phantom. The SF calculated from the scatter phantom in the MC simulation was 44%, the same as the SFconstant value. The average SF for the anthropomorphic phantom was 41%, but there was a maximum of 14 percentage points difference between each scan range, and the maximum difference in the SF was 8 percentage points for the difference in the source distribution. We constructed an MC simulation model which can calculate SFs for various phantoms. The SF was confirmed to be affected significantly by the source distribution. We judged that the actually measured SFconstant obtained from the PET scanner with the scatter phantom was not suitable for the assessment of the quality of all patient images.

Relationship between tumor volume and quantitative values calculated using two-dimensional bone scan images

The bone scan index (BSI) is calculated from a whole-body bone scan image; it shows the tumor burden in bone as a percentage of total skeletal mass. It has been used to determine the prognosis and to assess treatment effects; however, little has been reported on whether the BSI calculated using a two-dimensional image can accurately evaluate the three-dimensional spread in tumor volume. We investigated the relationship between tumor volume and BSI using Monte Carlo simulation (MCS). We simulated a gamma camera and constructed a voxel phantom based on an anthropomorphic phantom computed tomography (CT) image and gamma rays emitted from each part according to technetium-99m-labeled methylene diphosphonate (99mTc-MDP) uptake (bone 1, soft tissue 0.2, tumor 2–32). We constructed bone scan images from the obtained counts and analyzed them using the BSI calculation software. The BSI increased with increased tumor uptake (two- to 32-fold). However, there was not always a significant difference between change in BSI and tumor uptake of eight times or greater than that of bone. When BSI was calculated with a tumor having an uptake of four-to-eight times higher than that of bone, the BSI was consistent with tumor volume, but decreased to about half the tumor volume when tumors were in the thoracic spine (Th-spine) segment. The BSI can be a good indicator of tumor volume in most segments, even though it is affected by the tumor’s 99mTc-MDP uptake. Nevertheless, values calculated from the Th-spine should be interpreted carefully.

Development of a double-stranded siRNA labelling method by using 99mTc and single photon emission computed tomography imaging

Abstract In vivo biodistribution of small interfering RNAs (siRNAs) is important to develop them for medical use. Therefore, novel single photon emitter-labelled siRNA was prepared by using diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (DTPA) and poly(A) polymerase, and subsequently, real-time analysis of siRNA trafficking was performed by using single photon emission computed tomography (SPECT). This study aimed at assessing the use of 99mTc-radiolabelled siRNA targeting lacZ to detect lacZ expression in vivo. siRNA targeting lacZ was radiolabelled with 99mTc by using the bifunctional chelator DTPA, and the labelling efficiency and specific activity were determined. The probe stability in RNaseA was assessed. SPECT imaging was performed in mice overexpressing the lacZ gene in the liver. Radiolabelled siRNA remained highly stable in RNaseA solution at 37 °C. In SPECT imaging, significant 99mTc accumulation in the liver was observed in mice overexpressing the lacZ gene. 99mTc-labelled lacZ siRNA shows β-galactosidase-specific accumulation and appears promising for the visualisation of lacZ expression in vivo. Our labelled siRNA should be deliverable to specific regions overexpressing the target gene.

Abstract 438: Establishment of MDA-MB231-derived breast cancer cell lines possessing a higher metastatic activity and a resistance to radiation.

Background and purpose: Metastatic cancer tissues might have characteristics different from their original primary regions, which could affect strategies for radiotherapy. To investigate properties of metastatic cancers and their radiosensitivities, we established MDA-MB231-derived breast cancer cell lines, which were prone to cause metastasis when transplanted into mouse. Methods: A breast cancer cell line, MDA-MB231 expressing pGL4.5/luciferase were injected into nude mice via left ventricle or mammary gland tissue to form metastatic lesions. The metastatic cells in lymph nodes, bone, and lung were detected by a bioluminescence imaging technique, which were excised, cultured, and transplanted into the next mice in the same way. Such transplantation procedures were repeated 3 times to establish organ-oriented metastasis-prone cell lines. The different characteristics of these cells were examined by morphological analysis, and proliferation, invasion, and migration assays, as well as radiation sensitivity test. Result: There was no significant difference among cell lines in morphology and proliferative ability. All three metastasis-prone cell lines showed increased activity in migration and invasion compared to the parental cell line. Moreover, they showed lower sensitivities to radiation than the parental cell line, while no difference was found among the metastasis-prone cell lines. Conclusion: We have established new cell lines that could be used for the study of metastatic breast cancers in relation to the radiotherapy. Citation Format: Takamitsu Hara, Manabu Iwadate, Shuichi Shiratori, Kenji Gonda, Tatsuo Shimura, Yoshihiro Nakagami, Masahiko Shibata, Satoshi Waguri, Seiichi Takenoshita. Establishment of MDA-MB231-derived breast cancer cell lines possessing a higher metastatic activity and a resistance to radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 438. doi:10.1158/1538-7445.AM2013-438