Effects of Intratumoral Inflammatory Process on ¹⁸F-FDG Uptake: Pathologic and Comparative Study with ¹⁸F-Fluoro-α-Methyltyrosine PET/CT in Oral Squamous Cell Carcinoma

Abstract

The accurate depiction of both biologic and anatomic profiles of tumors has long been a challenge in PET imaging. An inflammation, which is innate in the carcinogenesis of oral squamous cell carcinoma (OSCC), frequently complicates the image analysis because of the limitations of 18 F-FDG and maximum standardized uptake values (SUV max ). New PET parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as 18 Ffluoro-α-methyltyrosine ( 18 F-FAMT), a malignancy-specific amino acid-based PET radiotracer, are considered more comprehensive in tumor image analysis. Here, we showed the substantial effects of the intratumoral inflammatory process on 18 F-FDG uptake and further study the possibility of MTV and TLG to predict both tumor biology (proliferation activity) and anatomy (pathologic tumor volume). Methods: 18 F-FDG and 18 F-FAMT PET images from 25 OSCC patients were analyzed. SUV max on the tumor site was obtained. PET volume computerized-assisted reporting was used to generate a volume of interest to obtain MTV and TLG for 18 F-FDG and total lesion retention (TLR) for 18 F-FAMT. The whole tumor dissected from surgery was measured and sectioned for pathologic analysis of tumor inflammation grade and Ki-67 labeling index. Results: The high SUV max of 18 F-FDG was related to the high inflammation grade. The SUV max ratio of 18 F-FDG to 18 F-FAMT was higher in inflammatory tumors (P , 0.05) whereas the corresponding value in tumors with a low inflammation grade was kept low. All 18 F-FAMT parameters were correlated with Ki-67 labeling index (P , 0.01). Pathologic tumor volume predicted from MTV of 18 F-FAMT was more accurate (R 5 0.90, bias 5 3.4 ± 6.42 cm 3 , 95% confidence interval 5 0.77-6.09 cm 3 ) than that of 18 F-FDG (R 5 0.77, bias 5 8.1 ± 11.17 cm 3 , 95% confidence interval 5 3.45-12.67 cm 3 ). Conclusion: 18 F-FDG uptake was overestimated by additional uptake related to the intratumoral inflammatory process, whereas 18 F-FAMT simply accumulated in tumors according to tumor activity as evaluated by Ki-67 labeling index in OSCC.

Peak of Standardized Uptake Value in Oral Cancer Predicts Survival Adjusting for Pathological Stage

“…The present findings also demonstrated that greater tumor size, p-SUVmax, p-MTV, p-TLG, which were poor predictors of OSCC (4,13,14), were significantly correlated with higher p-SUVpeak. Moreover, higher SUVpeak was significantly correlated with worse LRFS and DFS in this study, and we suggest that when SUVpeak is relatively high, more aggressive treatment strategies such as postoperative chemoradiotherapy are needed to improve survival outcomes.…”

Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection

“…While the basis underlying this weak but significant association is not clear, a possible link may be found in intratumoral inflammatory processes that can contribute to tumor FDG activity. [ 10 ] Infiltrating macrophages, granulocytes, and lymphocytes have been shown to elevate tumor FDG accumulation, especially when the cells are activated. [ 12 ] Conversely, many tumors can secrete inflammatory cytokines that promote systemic inflammation processes.…”

“…Since tumor FDG uptake is significantly influenced by intratumoral inflammatory processes, [ 10 ] it is tempting to speculate a relationship between this and hematologic predictors of cancer prognosis, but this possibility has not been previously explored. Conversely, the prognostic information provided by these parameters may be sufficiently independent, and therefore add incremental value to each other.…”

Specific transport of 3‐fluoro‐l‐α‐methyl‐tyrosine by LAT1 explains its specificity to malignant tumors in imaging

“…S1) was developed as a PET tracer for tumor imaging . In clinical studies, we and others have shown that [ 18 F]FAMT specifically accumulates in tumors and is useful for the prediction of prognosis, the assessment of therapy response and the differentiation of malignant tumors from inflammation and benign lesions . It has, therefore, been speculated that [ 18 F]FAMT is taken up by cancer cells via amino acid transporters specifically expressed in cancer cells.…”

“…(6) In clinical studies, we and others have shown that [ 18 F]FAMT specifically accumulates in tumors and is useful for the prediction of prognosis, the assessment of therapy response and the differentiation of malignant tumors from inflammation and benign lesions. (7)(8)(9)(10)(11)(12)(13)(14) It has, therefore, been speculated that [ 18 F] FAMT is taken up by cancer cells via amino acid transporters specifically expressed in cancer cells. The tumor uptake of [ 18 F] FAMT in PET is, in fact, well correlated with the level of expression of L-type amino acid transporter 1 (LAT1, SLC7A5) in various tumors, including non-small cell lung cancer, oral squamous cell carcinoma and esophageal cancer.…”