Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders?

Our plain-English summary of Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders?, by H.M. Zhuang, A. Cortés-Blanco, M. Pourdehnad, et al (Nuclear Medicine Communications, 2001).

The study

• Authors: H.M. Zhuang, A. Cortés-Blanco, M. Pourdehnad, L.E. Adam, A.J. Yamamoto, R. Martínez-Lázaro, J.H. Lee, J.C. Loman, M.D. Rossman, A. Alavi
• Journal: Nuclear Medicine Communications
• Published: 2001;22(10):1123-8
• Cited by: 79 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The association of hyperglycaemia with reduced fluorodeoxyglucose (FDG) uptake by tumour cells is well established. Therefore, it is standard practice that all patients must fast for at least several hours prior to FDG positron emission tomography (PET) imaging. However, the effect of hyperglycaemia on FDG uptake by inflammatory and infectious lesions is unknown. The aim of this study was to investigate this important issue.

Methods: For in vitro studies human mononuclear cells were isolated from 12 normal volunteers and FDG uptake was determined in medium containing differing concentrations of glucose. FDG uptake by human mesothelioma cells was also measured for comparison. For studies involving patients, 416 FDG PET scans of patients with confirmed malignancy (n=321) or benign lesions (n=95) were reviewed retrospectively. The relationship between serum glucose level and FDG uptake by the lesions was assessed utilizing the standardized uptake value (SUV) technique.

Results: In the in vitro studies, while FDG uptake by mesothelioma cells decreased as glucose concentration increased, there was no differential uptake of FDG uptake by mononuclear cells at glucose concentrations less than 250 mg x dl(-1). In clinical patients, FDG uptake by malignant lesions was slightly, but negatively affected by serum glucose level (r= -0.21, P<0.01) (glucose range 49-187 mg x dl(-1)). In contrast, FDG uptake by inflammatory lesions was positively associated with serum glucose level (r=0.43, P<0.01) (glucose range 54-215 mg x dl(-1)).

Discussion And Conclusion: While the degree of FDG uptake is primarily influenced by the nature of the underlying lesion, serum glucose concentration appears to have a small effect on FDG uptake, which differs between malignant disorders and inflammatory processes. Our data suggest that below a certain level, elevated glucose concentration might not have a negative effect on FDG uptake in inflammatory cells, contrary to that observed in malignant disorders.

In plain English

This study looked at whether blood sugar (glucose) levels affect how much of the tracer FDG is taken up on PET scans by cancers compared with inflamed or infected tissue. It did not study asbestos exposure. Its cancer comparisons involved a human malignant mesothelioma cell line and seven patients with mesothelioma. In laboratory tests, FDG uptake by mesothelioma cells fell as glucose rose from 50 to 200 mg/dl. Uptake by white blood cells from 12 healthy donors changed little between 50 and 250 mg/dl and fell above 250. The authors also reviewed 416 PET scans from patients without known diabetes: 321 with confirmed cancer and 95 with inflammatory or infectious conditions. In the cancer patients, higher glucose was linked with slightly lower uptake (r = -0.21). In the benign lesions, higher glucose was linked with higher uptake (r = 0.43), although the figure prints this value as negative. The authors concluded that mild to moderate high blood sugar may affect FDG uptake differently in malignant and inflammatory lesions. They noted that no diabetic patients were included.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiments on cells, combined with a retrospective review of patient PET scans
• Who was studied: In the laboratory: peripheral blood mononuclear cells from 12 healthy donors, and REN cells, a human malignant mesothelioma cell line. Among patients: 416 PET scans, covering 321 patients with malignant neoplasm (lung carcinoma n = 158, lymphoma n = 79, colorectal cancer n = 42, breast cancer n = 8, head and neck cancer n = 7, mesothelioma n = 7, melanoma n = 6, other malignancy n = 14) and 95 patients with painful lower limb arthroplasty (n = 71) or other known inflammatory or infectious conditions (n = 24). Of the 95 benign cases, 33 had infection and 62 had inflammation. No patients with known diabetes were included. The setting was the Hospital of the University of Pennsylvania, Philadelphia. Scan dates were not given.
• Exposure: Glucose concentration: in the culture medium for the cell experiments, and fasting serum glucose for patients (49 to 187 mg/dl in the cancer patients, 54 to 215 mg/dl in the benign group). Patients fasted at least 4 hours. No asbestos exposure was studied.
• Main results:
  • Mesothelioma (REN) cells: FDG uptake was greatest at the lowest glucose concentration (50 mg/dl) and decreased significantly from 50 to 200 mg/dl of glucose (P less than 0.0001).
  • Healthy donors' blood mononuclear cells: FDG uptake showed little change between 50 and 250 mg/dl glucose, increased slightly between 150 and 200 mg/dl, and decreased once glucose exceeded 250 mg/dl.
  • Patients with malignant lesions: FDG uptake was slightly, but negatively, affected by increasing serum glucose (r = -0.21, P less than 0.01).
  • Patients with inflammatory and infectious lesions: FDG uptake was slightly, but positively, affected by increasing serum glucose (r = 0.43, P less than 0.01). Figure 2 prints this value as R = -0.43.
  • Average SUV (mean plus or minus SD) of malignant lesions by glucose group: 7.68 plus or minus 3.37 (n = 31) below 80 mg/dl; 7.02 plus or minus 3.68 (n = 233) at 80 to 110 mg/dl; 5.11 plus or minus 2.51 (n = 57) above 110 mg/dl. The authors reported the highest-glucose group as significantly smaller than the other two (P less than 0.001).
  • Average SUV of benign lesions by glucose group: 3.13 plus or minus 1.69 (n = 14) below 80 mg/dl; 3.18 plus or minus 2.03 (n = 56) at 80 to 110 mg/dl; 5.28 plus or minus 3.13 (n = 25) above 110 mg/dl. The authors reported the highest-glucose group as significantly larger than the other two (P less than 0.01).
  • The average SUV from infectious lesions did not appear higher than that from inflammatory lesions. The data were not shown.
• The authors' conclusion: The authors concluded that mild to moderate hyperglycaemia may have a differential effect on FDG uptake by malignant versus inflammatory lesions.
• Limitations the authors state:
  • The cells from the 12 donors did not necessarily represent truly activated cells in the body.
  • No patients with diabetes were included, so a definite conclusion about diabetic patients cannot be drawn without further investigation.
  • The authors said data from animal models would ideally be needed to further confirm the findings.
  • Many factors other than glucose can affect FDG uptake among clinical patients.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, PET Scan.

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