Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Factors affecting tumor 18 F-FDG uptake in longitudinal mouse PET studies

Authors: Wei Sha, Hu Ye, Keisuke S Iwamoto, Koon-Pong Wong, Moses Quinn Wilks, David Stout, William McBride, Sung-Cheng Huang

Published in: EJNMMI Research | Issue 1/2013

Login to get access

Abstract

Background

Many biological factors of 2-[18 F]fluoro-2-deoxy-d-glucose (18 F-FDG) in blood can affect 18 F-FDG uptake in tumors. In this study, longitudinal 18 F-FDG positron emission tomography (PET) studies were performed on tumor-bearing mice to investigate the effect of blood glucose level and tumor size on 18 F-FDG uptake in tumors.

Methods

Six- to eight-week-old severe combined immunodeficiency mice were implanted with glioblastoma U87 (n = 8) or adenocarcinoma MDA-MB-231 (MDA) (n = 11) in the shoulder. When the tumor diameter was approximately 2.5 mm, a 60-min dynamic 18 F-FDG PET scan was performed weekly until the tumor diameter reached 10 mm. Regions of interests were defined in major organs and tumor. A plasma curve was derived based on a modeling method that utilizes the early heart time-activity curve and a late-time blood sample. The 18 F-FDG uptake constant K i was calculated using Patlak analysis on the tumors without an apparent necrotic center shown in the PET images. For each tumor type, the measured K i was corrected for partial volume (PV), and multivariate regression analysis was performed to examine the effects of blood glucose level ([Glc]) and tumor growth. Corrected Akaike's information criterion was used to determine the best model.

Results

The regression model that best fit the PV-corrected K i for U87 data was K i /RC = (1/[Glc]) × (0.27 ± 0.027) mL/min/mL (where [Glc] is in mmol/L), and for MDA, it was K i /RC = (0.04 ± 0.005) mL/min/mL, where K i /RC denotes the PV-corrected K i using an individual recovery coefficient (RC). The results indicated that 18 F-FDG K i /RC for U87 was inversely related to [Glc], while [Glc] had no effect on 18 F-FDG K i /RC of MDA. After the effects of PV and [Glc] were accounted for, the data did not support any increase of 18 F-FDG K i as the tumor (of either type) grew larger in size.

Conclusions

The effect of [Glc] on the tumor 18 F-FDG K i was tumor-dependent. PV- and [Glc]-corrected 18 F-FDG K i did not show significant increase as the tumor of either type grew in size.
Appendix
Available only for authorised users
Literature
1.
Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett S, Phelps ME, Herschman H, Czernin J, Weber W: Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 2006,12(19):5659–5667. 10.1158/1078-0432.CCR-06-0368CrossRefPubMed
2.
Murayama C, Harada N, Kakiuchi T, Fukumoto D, Kamijo A, Kawaguchi AT, Tsukada H: Evaluation of D - 18  F-FMT, 18  F-FDG, L - 11 C-MET, and 18  F-FLT for monitoring the response of tumors to radiotherapy in mice. J Nucl Med 2009,50(2):290–295. 10.2967/jnumed.108.057091CrossRefPubMed
3.
4.
Adams MC, Turkington TG, Wilson JM, Wong TZ: A systematic review of the factors affecting accuracy of SUV measurements. Am J Roentgenol 2010,195(2):310–320. 10.2214/AJR.10.4923CrossRef
5.
Krak NC, van der Hoeven JJM, Hoekstra OS, Twisk JWR, van der Wall E, Lammertsma AA: Measuring FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging 2003,30(5):674–681. 10.1007/s00259-003-1127-zCrossRefPubMed
6.
Wong CO, Thie J, Parling Lynch KJ, Zakalik D, Margolis JH, Gaskill M, Hill J, Qing F, Fink-Bennett D, Nagle C: Glucose-normalized standardized uptake value from 18 F-FDG PET in classifying lymphomas. J Nucl Med 2005,46(10):1659–1663.PubMed
7.
Torizuka T, Clavo AC, Wahl RL: Effect of hyperglycemia on in vitro tumor uptake of tritiated FDG, thymidine. L -methionine and L -leucine. J Nucl Med 1997,38(3):382–386.PubMed
8.
Stahl A, Ott K, Schwaiger M, Weber WA: Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET. European J Nuclear Med Molecul Imagin 2004,31(11):1471–1478. 10.1007/s00259-004-1626-6CrossRef
9.
Hadi M, Bacharach SL, Whatley M, Libutti SK, Straus SE, Rao VK, Wesley R, Carrasquillo JA: Glucose and insulin variations in patients during the time course of a FDG-PET study and implications for the ''glucose-corrected'' SUV. Nucl Med Biol 2008,35(4):441–445. 10.1016/j.nucmedbio.2008.02.007CrossRefPubMed
10.
Torizuka T, Fisher SJ, Wahl RL: Insulin-induced hypoglycemia decreases uptake of 2-[F-18]fluoro-2-deoxy- D -glucose into experimental mammary carcinoma. Radiology 1997, 203: 169–172.CrossRefPubMed
11.
Wong KP, Sha W, Zhang X, Huang SC: Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18  F-FDG in mice. J Nucl Med 2011,52(5):800–807. 10.2967/jnumed.110.085092CrossRefPubMed
12.
Ferl GZ, Zhang X, Wu HM, Huang SC: Estimation of the 18  F-FDG input function in mice by use of dynamic small-animal PET and minimal blood sample data. J Nucl Med 2007,48(12):2037–2045. 10.2967/jnumed.107.041061CrossRefPubMed
13.
Barrett PHR, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, Foster DM: SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism 1998,47(4):484–492. 10.1016/S0026-0495(98)90064-6CrossRefPubMed
14.
Patlak CS, Blasberg RG, Fenstermacher J: Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983, 3: 1–7. 10.1038/jcbfm.1983.1CrossRefPubMed
15.
Huang SC, Phelps ME, Hoffman EJ, Sideris K, Selin CJ, Kuhl DE: Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 1980, 238: E69-E82.PubMed
16.
Spence AM, Muzi M, Graham MM, O'Sullivan F, Krohn KA, Link JM, Lewellen TK, Lewellen B, Freeman SD, Berger MS, Ojemann GA: Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant. J Nucl Med 1998,39(3):440–448.PubMed
17.
Lindstrom MJ, Bates DM: Nonlinear mixed effects models for repeated measures data. Biometrics 1990, 46: 673–687. 10.2307/2532087CrossRefPubMed
18.
Pinheiro J, Bates D, DebRoy S, Sarkar D, the R Development Core Team: nlme: linear and nonlinear mixed effects models. R package version 3. 2013, 1–109.
19.
Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA: Impact of animal handling on the results of 18  F-FDG PET studies in mice. J Nuclear Med 2006,47(6):999–1006.
20.
Diederichs CG, Staib L, Glatting G, Beger HG, Reske SN: FDGPET: elevated plasma glucose reduces both uptake and detection rate of pancreatic malignancies. J Nucl Med 1998,39(6):1030–1033.PubMed
21.
Higashi K, Clavo AC, Wahl RL: In vitro assessment of 2-fluoro-2-deoxy- D -glucose, L -methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med 1993,34(5):773–779.PubMed
22.
Zander T, Scheffler M, Nogova L, Kobe C, Engel-Riedel W, Hellmich M, Papachristou I, Toepelt K, Draube A, Heukamp L, Buettner R, Ko YD, Ullrich RT, Smit E, Boellaard R, Lammertsma AA, Hallek M, Jacobs AH, Schlesinger A, Schulte K, Querings S, Stoelben E, Neumaier B, Thomas RK, Dietlein M, Wolf J: Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [ 18  F]fluorodeoxyglucose and [ 18  F]fluorothymidine positron emission tomography. J Clinic Oncol 2011,29(13):1701–1708. 10.1200/JCO.2010.32.4939CrossRef
23.
Soret M, Bacharach SL, Buvat I: Partial-volume effect in PET tumor imaging. J Nuclear Med 2007,48(6):932–945. 10.2967/jnumed.106.035774CrossRef
24.
Sha W, Iwamoto K, McBride W, Huang SC: Effects of glucose and free fatty acid levels on in vitro 18 F-FDG uptake in tumor cells. J Nucl Med 2011, 52: 602.
25.
Allen LA, Gerritsen ME: Regulation of hexose transport in cultured bovine retinal microvessel endothelium by insulin. Experiment Eye Res 1986,43(4):679–686. 10.1016/S0014-4835(86)80034-3CrossRef
26.
Zeng G, Quon MJ: Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest 1996,98(4):894–898. 10.1172/JCI118871CrossRefPubMed
27.
Lee KH, Ko BH, Paik JY, Jung KH, Choe YS, Choi Y, Kim BT: Effects of anesthetic agents and fasting duration on 18 F-FDG biodistribution and insulin levels in tumor-bearing mice. J Nucl Med 2005, 46: 1531–1536.PubMed
Metadata
Title
Factors affecting tumor 18 F-FDG uptake in longitudinal mouse PET studies
Authors
Wei Sha
Hu Ye
Keisuke S Iwamoto
Koon-Pong Wong
Moses Quinn Wilks
David Stout
William McBride
Sung-Cheng Huang
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-51

Other articles of this Issue 1/2013

EJNMMI Research 1/2013 Go to the issue

Original research

Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction

Original research

Evaluation of androgen-induced effects on the uptake of [18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model

Original research

Bone Scan Index: a prognostic imaging biomarker for high-risk prostate cancer patients receiving primary hormonal therapy

Short communication

Foot skin depots of 18F-fluorodeoxyglucose do not enable PET/CT lymphography of the lower extremity lymphatic system in man

Original research

Evaluation of the biodistribution and radiation dosimetry of the 18F-labelled amyloid imaging probe [18F]FACT in humans

Original research

Influence of d-glutamine and d-glutamic acid sequences in optical peptide probes targeted against the cholecystokinin-2/gastrin-receptor on binding affinity, specificity and pharmacokinetic properties