Usefulness of (18)F-fluorodeoxyglucose PET for radiosurgery planning and response monitoring in patients with recurrent spinal metastasis.

INTRODUCTION: With the advancement and successful treatment of metastatic spinal cord disease, newer treatments are needed for the long-term survivors of recurrent disease. The lack of a standardized re-treatment regimen and the difficulty in delineating the tumor margins among patients who have received the treatment with metallic spinal fixation and conventional radiation are two of the challenges to be faced in recurrent metastatic spinal cord disease. In these patients, we applied hypofractionated stereotactic radiosurgery by defining the tumor margin with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). PATIENTS AND METHODS: Three consecutive recurrent spinal metastasis patients underwent the CyberKnife treatment (Accuray, Inc., Sunnyvale, CA) from March 2004 to July 2004. A three-fraction schedule was applied at approximately 24 hour intervals. One patient had sarcoma and the other two patients had breast cancer. All patients had received previous conventional radiotherapy after operation ranging from 30 Gy to 45 Gy. CT-based planning was corrected by the FDG-PET hyperuptake area with the help of nuclear medicine. The mass responses were followed not only by MRI but also by FDG-PET, which was taken prior to treatment, and at one and six months after the treatment. The changes in standard uptake value (SUV) of serial PET were taken as a measure of response. To evaluate the relative SUV changes from different pretreatment values, we set a reduction index (RI), which represents the ratio of SUV change to pretreatment SUV. RESULTS: No significant complications were noted during treatment with a mean follow-up of 13.3 months. The tumor volume on CT-based planning was 2.2 times larger than that of the CT-PET combined planning in case 1 of paraspinal muscle invasion. But the tumor volumes showed minimal changes in the other cases, in which the metastatic tumors were confined to the vertebral bodies. The SUV one month after treatment showed variable decreases and the RI ranged from 0.07 to 0.7. However, the SUVs at 6 months were well correlated with the clinical results. One patient showed marginal failure and the other two patients showed local control of the tumor, as their RI values were 0.65 and 0.87, respectively. CONCLUSION: To our knowledge, this is the first report using FDG-PET with radiosurgery in patients with recurrent spinal metastases hidden under metallic artifacts. The mass responses measured by SUV changes in FDG-PET correlated with the clinical results.

A microdosimetric approach to the thermal neutron fluence prescription for clinical BNCT.

A microdosimetric estimation has been performed to investigate the stochastic variations in doses to the target cell nuclei in boron neutron capture therapy (BNCT). The 9L gliosarcoma cells and the capillary endothelial cells were the targets of our interest. More than 80% of tumour control and less than 50% of myeloparesis incidence were taken as the biological endpoints to be accomplished. Estimation was performed for two major boron carriers, sulfhydryl borane (BSH) and boronophenylalanine (BPA). From the macrodosimetric point of view, the effective thermal neutron fluence in BNCT ranges from 3.96 x 10(12) to 5.17 x 10(12). From the microdosimetric point of view however, the prescription regarding thermal neutron irradiation becomes much more complex. According to the microdosimetric analysis, the difference between the tumour and the normal tissue in BSH or BPA concentration is not large enough to guarantee the 80% control of 9L gliosarcoma along with the myeloparesis incidence limited below 50%.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis is dependent on activation of cysteine and serine proteases.

We examined the role of caspases and serine protease(s) in cell death induced by tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). After incubation of adenocarcinoma cells with TRAIL, caspase-3, -8 were activated and the cleavage of Bid induced the release of cytochrome c, from the mitochondria to the cytosol. Tetrapeptide inhibitors of caspase-1, -2, -3, and -8 suppressed DNA fragmentation and attenuated the release of cytochrome c, whereas inhibitors of caspase-5 did not. Interestingly, the general serine protease(s) inhibitor 4-(2-aminoethyl)benzylsulfonyl fluoride (AEBSF) resulted in the arrest of apoptosis. However, the AEBSF did not prevent the release of mitochondrial cytochrome c during TRAIL-induced apoptosis. From these results, we postulate that serine protease(s) may be involved in post-mitochondrial apoptotic events, that lead to the activation of the initiator, caspase-9.

Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines.

The recent development and refinement of cDNA array and genechip techniques allows for large-scale parallel screening of gene expression and thereby provides a global assessment of molecular events transpiring in cell populations. We hypothesized that such an approach might help illuminate current issues in glioma research. To what degree are glioblastoma multiforme (GBM) cell lines representative of primary GBM tumors? We carried out a gene expression profiling study using cDNA array technology on 10 GBM primary tissues and 3 GBM cell lines. The gene expression levels were quantified, and the within-subject ranks of the gene expression levels were subsequently evaluated by hierarchical clustering analysis, multidimensional scaling analysis, and principal component analysis. Hierarchical cluster analysis shows that the 3 cell lines form one main cluster and the 10 tissue samples form a separate cluster. Multidimensional scaling and principal components analysis provided further graphical demonstration that the cell lines are clearly different from the tissue samples and that the cell lines are more different between themselves than are the tissues.

Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on medulloblastoma cell line, Daoy, harboring mutant p53.

To improve the survival rate, gene therapy, such as the replacement of inactivated tumor suppressor genes, has become a new investigational adjuvant treatment modality for human malignancies. We investigated the effect of adenovirus(Ad)-mediated transfer of wildtype p53 tumor suppressor gene on the medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50 multiplicity of infection (moi), immunohistochemical staining with p53 monoclonal antibody showed positive staining in all cells 2 days after Ad-CMV-p53 infection. The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected cells, and expression of wild-type p53 protein peaked on day 2 after the infection. The growth of Ad-CMV-p53-infected cells was greatly suppressed in vitro, and the Ad-CMV-p53 treatment significantly reduced the tumor mass in vivo. The mean weight of Ad-CMV- infected tumors was only 16% of those which were mock infected, and 25% of those which were Ad-CMV-beta-gal infected. On microscopic examination, Ad-CMV-p53-infected tumors showed numerous apoptotic bodies. This Ad-CMV-p53 gene transfer showed high transduction efficacy and expression, resulting in significant growth inhibition of Daoy harboring mutant type p53.

Protein kinase C activation by PMA rapidly induces apoptosis through caspase-3/CPP32 and serine protease(s) in a gastric cancer cell line.

Phorbol 12-myristate 13-acetate (PMA) rapidly induced cell death in SNU-16 gastric adenocarcinoma cells. DNA ladder formation and caspase-3/CPP32 activation were observed in PMA treated cells indicating that PMA induces apoptosis. z-DEVD-fmk, specific inhibitor of caspase-3/CPP32, inhibited the induction of apoptosis by PMA, demonstrating that caspase/CPP32 are critically involved in PMA-induced apoptosis. The serine protein inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride effectively blocked apoptosis, and also prevented caspase-3/CPP32 activation. Go6983, a specific inhibitor of PKC, almost completely suppressed apoptosis and caspase-3/CPP32 activation. Furthermore, 1,2-dihexanoyl-sn-glycerol, an endogenous activator of PKC, induced apoptosis detected by DNA fragmentation and Hoechst 33258 nuclear staining. From these results, we conclude that PMA is not only a tumor promoter, but can also induce apoptosis in gastric cancer cells. PMA-induced apoptosis appears to be mediated through activation of protein kinase C, and the activation of serine protease(s) and caspase-3/CPP32 may be the molecular mechanisms by which PMA induces apoptosis.

Predictors for benign solitary pulmonary nodule in tuberculosis-endemic area.

BACKGROUND: Solitary pulmonary nodule (SPN) may show different presentation in tuberculosis (TB)-endemic countries. The aim of this study was to identify clinical and radiological predictors favoring benign or malignant SPN in TB-endemic region. METHODS: Two hundred one SPNs in 201 consecutive Korean patients were included (< 3 cm in diameter, all confirmed by pathology or bacteriology, 93 benign and 108 malignant diseases). For clinical parameters, age, sex, smoking status and amount, and past history of pulmonary tuberculosis and diabetes mellitus were investigated retrospectively. For radiological parameters, size, location, margin characteristics, presence of calcification, pleural tag, surrounding satellite nodule, cavitation, internal low attenuation, open bronchus sign, surrounding ground-glass opacity, enhancement pattern of the SPNs and mediastinal lymph node (LN) enlargement were analyzed on chest CT scans. RESULTS: Patients with a older age (60.7 +/- 9.6 vs 56.2 +/- 13.1, p = 0.008) and more than 40-pack years smoking (27.8% vs 14.0%, p = 0.017) were more frequently related with malignant than benign SPN. On chest CT scans, spiculated margin, contrast enhancement more than 20 Hounsfield unit and presence of pleural tag and mediastinal LN enlargement were more frequently observed in malignant than benign SPNs. In contrast to previous studies, satellite lesions (21.5% vs 1.9%, p < 0.001) and cavitation (20.4% vs 5.6%, p = 0.001) were more frequently seen in benign than malignant SPN. Positive predictive values of benignity were 90.9% and 76.0%, respectively, when satellite lesions and cavitation were found in cases of SPN. CONCLUSION: Satellite lesions and cavitation on chest CT scan could be useful predictors for benign SPN in TB-endemic areas.

Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95-independent manner in human gastric adenocarcinoma cells.

We investigated the mechanism of mitomycin C (MMC)-induced apoptosis in SNU-16 human gastric adenocarcinoma cells. Caspase-8 and caspase-3 were activated in MMC-treated cells whereas caspase-1 was not activated, and cytochrome c was released from mitochondrial membrane to cytosol suggesting that caspase-9 was activated during the MMC-induced apoptotic process. Protein kinase C (PKC) delta was cleaved to its characteristic 40 kDa fragment in a caspase-3-dependent manner; on the other hand PKC zeta was cleaved to approximately 40 kDa independently of caspase-3 in the drug-induced apoptosis of the cells. Incubation with z-DEVD-fmk and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk) almost completely abrogated MMC-induced DNA fragmentation, indicating that activation of these caspases was crucially involved in MMC-induced apoptosis. Activation of caspase-8 in response to Fas triggering by recruitment of caspase-8 to the Fas has also been found, however, MMC did not induce FasL and Fas expression, as evidenced by reverse transcriptase-polymerase chain reaction and Western blotting. Taken together, these findings indicate that MMC-induced apoptosis in SNU-16 cells was mediated by caspase-8, caspase-9, and caspase-3 activation independently of FasL/Fas interactions.

Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells.

To elucidate possible mechanisms of phorbol 12-myristate 13-acetate (PMA) induced in vitro invasiveness of glioblastoma cells, we examined expression levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using Western blotting and gelatin zymography assay, and found that PMA induced the secretion of MMP-9, activated MMP-2 proenzyme to fully active form of 59 kDa, down-regulated the TIMP-1 and TIMP-2 secretion, and increased MT1-MMP on the cell surface. However, PKC inhibitor Go 6983 reversed all of these effects brought about by PMA. We, therefore, conclude the activation of PKC by PMA in these cells plays a critical role in the regulation of MMPs/TIMPs system, which has a major role in tumor invasion and metastasis.

Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression.

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.

Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling.

We carried out a gene expression profiling study using cDNA array technology with 24 primary glioma tissues of low-grade (oligodendroglioma), intermediate-grade (anaplastic oligodendroglioma and anaplastic astrocytoma), and high-grade (glioblastomas multiforme) tumors and found that insulin-like growth factor binding protein 2 (IGFBP2) was consistently overexpressed only in glioblastoma multiforme. The cDNA array results were confirmed by Northern and Western blotting. The fact that the IGFBP2 gene, which is normally expressed in fetal cells and turned off in adult cells, becomes reactivated in the most advanced stage of glioma suggests that glioma progression is a result of dedifferentiation or results from a block of differentiation. Identification of IGFBP2 as a gene associated with glioma progression demonstrates the power and utility of high-throughput gene expression profiling in cancer gene discovery.

cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines.

Tumor cell lines are an indispensable tool for cancer research. However, among cell lines of the same pathological group, heterogeneity has been detected in gene expression, gene mutation, and cellular response to various treatments. In this study, we systematically investigated the extent of heterogeneity of gene expression in three glioblastoma cell lines using cDNA array technology in which the expression of 588 cellular genes is studied simultaneously. Comparison of the expression profiles revealed substantial qualitative and quantitative heterogeneity. Among the 588 genes, 197 genes were expressed in all three lines and 56 genes were not expressed in any of the three lines; total of 222 genes were expressed in only two of the three cell lines, and 113 genes were expressed in only one of the three cell lines. These results provide molecular evidence that cell lines of the same pathological origin can be highly heterogeneous.

Characterization of cellular pathways involved in glioblastoma response to the chemotherapeutic agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by gene expression profiling.

The effectiveness of chemotherapy for human cancers is limited by pharmacokinetic parameters such as variation in metabolism and is determined by the cellular response. In this work, we aimed to gain a more holistic understanding of the molecular basis of glioma response to the DNA-alkylating agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by using a systematic approach: we investigated the expression of 588 genes with various cellular functions in a BCNU-resistant glioblastoma cell line and a BCNU-sensitive subline before and after treatment with BCNU. Our gene expression profiling revealed major differences in gene expression between these two cell lines, especially after treatment with BCNU. One striking example was that BCNU decreased the expression of six DNA-repair genes in sensitive but not in resistant cells. In sensitive cells, BCNU treatment resulted in the induction of two MAP kinase genes; this finding suggests that the specific response to BCNU in sensitive cells may involve the Jun kinase signal transduction pathway. After BCNU treatment, marked induction of tumor necrosis factor was detected only in sensitive cells, suggesting that tumor necrosis factor is a mediator of BCNU-induced cell death. Bcl-2 family members were not altered by BCNU in sensitive cells, suggesting that BCNU-induced cell death may be independent of the bcl-2 pathway. Results of the present study demonstrate that gene expression profiling may facilitate identification of cellular pathways associated with specific responses to chemotherapeutic agents and contribute to an understanding of the molecular basis of drug action.

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings.

OBJECTIVE: The purpose of our study was to describe high-resolution CT findings of nonspecific interstitial pneumonia with fibrosis and to compare findings seen on CT with pathologic findings. MATERIALS AND METHODS: High-resolution CT findings of biopsy-proven non-specific interstitial pneumonia with fibrosis from 23 consecutive patients (one man and 22 women) were analyzed retrospectively by two chest radiologists. CT findings were compared with pathologic findings. RESULTS: The predominant high-resolution CT finding, seen in all patients, was bilateral patchy areas of ground-glass opacity with (35%) or without (65%) areas of consolidation. Irregular linear opacities (87%), thickening of bronchovascular bundles (65%), and bronchial dilatation (52%) were also frequently seen. Honeycombing was not seen in any patient. All parenchymal abnormalities showed subpleural predominance. Areas of ground-glass opacity with or without irregular linear opacity or bronchial dilatation on CT corresponded pathologically to areas of interstitial thickening caused by varying degrees of interstitial inflammation and fibrosis showing temporal uniformity. Areas of consolidation, seen at five biopsy sites, represented the areas of bronchiolitis obliterans organizing pneumonia, foamy cell collections in alveolar spaces, or microscopic honeycombing with mucin stasis. CONCLUSION: On high-resolution CT, nonspecific interstitial pneumonia with fibrosis is most commonly revealed as patchy subpleural areas of ground-glass opacity mixed with irregular linear opacity or bronchial dilatation. These areas represent interstitial thickening caused by varying degrees of interstitial inflammation, fibrosis, or both.

Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array.

The profiling of differentially expressed genes from primary tumor samples using cDNA expression array can reveal new tumor markers as well as target genes for therapeutic intervention. Using cDNA expression array technology, we produced an expression profile of genes that are associated with human cervical cancer. Hybridization of the cDNA blotting membrane (588 genes on a single membrane) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either normal cervix or cervical cancer. Parallel analyses of the hybridized signals enabled us to profile genes that were differentially expressed in cervical cancer. In each experiment, the extent of hybridization of each gene was evaluated by comparison with the most abundant mRNAs in the human cervix. These include myc proto-oncogene, 40S ribosomal protein S19, heat shock proteins, leukosialin S (CD43), integrin alphaL (CD11A), calgranulin (A), and CDK4 inhibitor (p16ink4). No detectable changes were observed in the expression levels of these genes. Several mRNAs, such as those encoding guanine nucleotide-binding protein Gs (alpha subunit), leukocyte adhesion protein (LFA1-beta), nuclear factor NF45, homeobox protein Hox-A1, and beta-catenin were detected in increased levels in cervical cancer. Genes that showed decreased expression in cervical cancer tissue were a group of apoptosis-related proteins, cell adhesion molecules, nuclear transcription factors, and a homeobox protein (Hox7). For example, the expression levels of Smad1 and Hox7 were consistently decreased in all tumor tissues tested. Northern analysis of Smad1 and Hox7 RNA in primary cervical tumor tissues and cervical carcinoma cell lines indicated that, in general, the mRNA levels of these genes were decreased in human cervical cancer. The precise relationship between the altered expression of these genes and cervical tumorigenesis is a matter of further investigation.

Increased uptake of 99mTc-HMPAO in necrotic brain tumors.

99mTc complex of hexamethylpropylene amine oxime (99mTc-HMPAO), which has been used as a tracer for regional cerebral blood flow (rCBF), has been shown to localize in primary brain tumors with wide spectrum of its uptake. The causes of the wide spectrum of tumor uptake, however, has not been understood in detail. We performed autoradiographic study with this agent to get further knowledge about HMPAO distribution in 10 cases of transplanted rat gliomas. Eight cases of rat gliomas without tumor necrosis, showed decreased uptake of 99mTc-HMPAO in the autoradiography (average tumor/normal (T/N) uptake ratio: 0.75, range: 0.40-0.90). On the other hand, two cases with tumor necrosis revealed increased uptakes of this agent in central necrotic area. T/N uptake ratios of these two cases were 1.23 and 1.42, respectively. In addition, three patients with histologically proven glioblastoma with tumor necrosis were studied after administration of 20mCi 99mTc-HMPAO. Two out of three patients showed higher uptake of 99mTc-HMPAO in tumor necrotic area than the contralateral area. Our findings suggest that the necrotic area of brain tumor may retain 99mTc-HMPAO and causes an increased uptake.

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation.

In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

Localized form of bronchioloalveolar carcinoma: FDG PET findings.

OBJECTIVE: The aim of our study was to describe 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings of a localized form of bronchioloalveolar carcinoma and to compare those findings with other cell types of lung cancer. SUBJECTS AND METHODS: FDG PET was performed in 48 patients with lung cancer. The patients had carcinomas of various cell types: bronchioloalveolar carcinoma (n = 9), squamous cell carcinoma (n = 11), adenocarcinoma (n = 22), and other cell types (n = 6). Using FDG PET, we compared peak standardized uptake values among the various cell types of lung cancer. CT and pathologic findings for patients with bronchioloalveolar carcinoma were also reviewed. RESULTS: Overall, 48 malignant tumors showed a mean peak standardized uptake value of 8.0 +/- 4.1. The mean peak standardized uptake value was 3.5 +/- 2.2 for bronchioloalveolar carcinoma, 10.8 +/- 4.4 for squamous cell carcinoma, and 8.8 +/- 3.2 for adenocarcinoma. The mean peak standardized uptake value for bronchioloalveolar carcinoma was significantly lower than that for adenocarcinoma and squamous cell carcinoma (p < .001). On high-resolution CT scans, bronchioloalveolar carcinomas appeared as areas of ground-glass opacity (n = 4), as nodules (n = 2), as masses (n = 2), and as a ground-glass opacity plus consolidation (n = 1). On pathologic examination, bronchioloalveolar carcinomas were well differentiated, having moderate degrees of nuclear atypism, mild degrees of mitotic figure, desmoplasia, and necrosis. CONCLUSION: The localized form of bronchioloalveolar carcinoma shows significantly lower peak standardized uptake values than do other lung carcinomas. Thus, bronchioloalveolar carcinoma can be a potential cause of false-negative findings of malignancy on FDG PET scans. When bronchioloalveolar carcinoma is suggested, FDG PET results should be interpreted in combination with high-resolution CT findings.