Molecular Mechanism Underlying the Detection of Colorectal Cancer by 18F-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography

Izuishi, Kunihiko; Yamamoto, Yuka; Sano, Takanori; Takebayashi, Ryusuke; Nishiyama, Yoshihiro; Mori, Hideki; Masaki, Tsutomu; Morishita, Asahiro; Suzuki, Yasuyuki

doi:10.1007/s11605-011-1727-z

Cited by 31 publications

(21 citation statements)

References 26 publications

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“…The increased energy provided by GLUT1 overexpression likely plays a role in both HCC and Meta tumor growth; therefore, the reason for the contrasting PCNA results is unclear. However, the PCNA expression in Meta specimens was consistent with a previous study (20). These results indicate that SUV cannot always estimate tumor growth or prognosis in the patients with liver metastasis of colorectal cancer.…”

Section: Discussionsupporting

confidence: 90%

“…Reverse transcription was carried out with 1 µg RNA, and the resulting cDNA was analyzed by real-time PCR with Power SYBR Green PCR Master Mix and the ABI Prism 7000 (Applied Biosystems, Foster, CA, USA). Target-specific oligonucleotide primers and probes were previously described (19,20). As endogenous control, the amplification of 18S rRNA was used.…”

Section: Methodsmentioning

confidence: 99%

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Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

et al. 2013

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To elucidate the molecular mechanisms underlying the insufficient sensitivity in the detection of hepatocellular carcinoma (HCC) by [18F] 2-ﬂuoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), the characteristics of glucose metabolism-related protein expression in HCC were examined in liver metastasis from colorectal cancer (Meta). Thirty-four patients (14 Meta and 20 HCC) who underwent FDG-PET and hepatectomy were studied. The relationships between the maximum standardized uptake value (SUV) in tumors and the mRNA expression of glucose metabolism-related proteins [hexokinase (HK), glucose transporter 1 (GLUT1), and glucose-6-phosphatase (G6Pase)] and proliferating cell nuclear antigen (PCNA) were examined in snap-frozen specimens with quantitative PCR. Tumor detection rates were lower in HCC (15/20) compared to Meta (13/14) patients. HK and GLUT1 expression was lower and G6Pase expression was higher in HCC compared to Meta. In particular, GLUT1 overexpression was 92-fold in Meta and 11-fold in HCC compared to the surrounding liver. The SUV correlated with GLUT1 and PCNA expression in HCC, but not Meta patients. Of note, four cases of poorly differentiated (P/D) HCC compared to moderately differentiated (M/D) HCC produced completely different results for FDG uptake (SUV, 14.4 vs. 4.0) and mRNA expression (G6Pase expression, 0.007 vs. 1.5). Variations in the expression of glucose metabolism-related enzymes between HCC and Meta patients are attributed to origin or degree of differentiation. Low FDG uptake in M/D HCC reflected low GLUT1 and high G6Pase expression, while high FDG accumulation in P/D HCC could reflect increased GLUT1 and decreased G6Pase expression. These results may explain why M/D HCC is not detected as sensitively by FDG-PET.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

et al. 2013

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“…The expression of HIF-1α and the correlated target genes, including Glut-1, is regulated by the PI3K/protein kinase B (Akt) pathway (23,24). However, it remains unclear whether the PI3K/Akt signal pathway is involved in the regulation of FDG uptake (15,16,25,26). Consequently, the association between FDG and hypoxia markers must be studied further.…”

Section: Introductionmentioning

confidence: 99%

Fluorodeoxyglucose uptake in laryngeal carcinoma is associated with the expression of glucose transporter-1 and hypoxia-inducible-factor-1α and the phosphoinositide 3-kinase/protein kinase B pathway

et al. 2014

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High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is believed to be an intrinsic marker of hypoxia in malignant tumors. The expression of hypoxia-inducible factor-1α (HIF-1α) and correlated target genes, including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling pathway is involved in regulating FDG uptake directly. In the present study, 24 consecutive patients with laryngeal carcinoma were examined pre-operatively and the standardized uptake values (SUV) of the laryngeal carcinomas were determined. Glut-1, HIF-1α, PI3K and phosphorylated-Akt (p-Akt) expression was detected by immunohistochemical staining of paraffin sections from the tumor specimens. Associations among SUVmax, Glut-1, HIF-1α, PI3K and p-Akt protein expression and the other clinical parameters were analyzed. The univariate analyses revealed a significantly shorter survival time along with higher HIF-1α (P=0.018) and PI3K (P=0.008) expression, but the survival time was not significantly correlated with Glut-1 or p-Akt expression. The multivariate analysis demonstrated that higher SUVmax (P=0.043) and PI3K expression (P=0.012) were significantly correlated with a poor survival time. Spearman’s rank analysis showed significant correlations between SUVmax and HIF-1α (r=0.577; P=0.003), PI3K (r=1.0; P<0.0001) and p-Akt (r=0.577; P=0.003) expression. PI3K was associated with poorly- and moderately-differentiated laryngeal carcinoma (P=0.012). In conclusion, a high SUVmax indicates a poor prognosis for laryngeal carcinoma. Also, a high SUVmax may be associated with the increased expression of Glut-1, HIF-1α, PI3K and p-Akt.

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“…On the other hand, KRAS mutants with low SUV, high MPP, and high BF demonstrated increased mcm2 expression, implying a proliferative phenotype. Unlike some tumors, previous data indicate that 18 F-FDG uptake in primary CRC is unrelated to proliferation (32) whereas a recent study has shown that induction of proliferation in CRC tissue samples did not increase 18 F-FDG uptake (although induction of HIF-1 did increase SUV) (33). Thus, there is concordance between the histologic and imaging findings for both of these subgroups of KRAS mutants.…”

Section: Discussionmentioning

confidence: 77%

Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

et al. 2014

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This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. Methods: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: 18 F-FDG uptake ( 18 F-FDG maximum standardized uptake value [SUV max ]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. Results: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high 18 F-FDG SUV max and low MPP showed greater frequency of HIF-1 expression (P 5 0.032). KRAS mutants with low 18 F-FDG SUV max , high MPP, and high blood flow expressed mcm2 (P 5 0.036). Conclusion: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor 18 F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

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Molecular Mechanism Underlying the Detection of Colorectal Cancer by 18F-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography

Cited by 31 publications

References 26 publications

Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

Fluorodeoxyglucose uptake in laryngeal carcinoma is associated with the expression of glucose transporter-1 and hypoxia-inducible-factor-1α and the phosphoinositide 3-kinase/protein kinase B pathway

Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

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