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18F-Fludeoxyglucose (FDG)

18f-fludeoxyglucose (FDG) Structural Formula

2-deoxy-2-[18F]fluoro-D-glucose (FDG) is a radiolabeled imaging agent that has been approved by the FDA for the following three indications:

  • Fludeoxyglucose F 18 Injection is indicated in positron emission tomography (PET) imaging for assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
  • Fludeoxyglucose F 18 Injection is indicated in PET imaging in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging, for the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function.
  • Fludeoxyglucose F 18 Injection is indicated in PET imaging in patients for the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.

There is also a long history of using FDG in studies assessing malignancy, epilepsy, dementia, inflammation/infection imaging, and many other diseases. There are thousands of studies that have been published using this most commonly used PET imaging agent.

FDG is transported from blood to tissues in a manner similar to glucose and competes with glucose for hexokinase phosphorylation to FDG-6-phosphate. Since FDG-6-phosphate is not a substrate for subsequent glucose metabolic pathways and has a very low membrane permeability, the FDG-6-phosphate becomes trapped in tissue in proportion to the rate of glycolysis or glucose utilization of that tissue [Reivich 1979, Yonekura 1982, Schelbert 1982, Doyle 1987, Joensu 1987, Berry 1991, Bonow 1991, Maisey 1991, Hawkins 1991, Schwaiger 1991].


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Berry JJ, Baker JA, Pieper KS, et al. The effect of metabolic milieu on cardiac PET imaging using fluorine-18-deoxyglucose and nitrogen-13-ammonia in normal volunteers. J Nucl Med 1991; 32: 1518-1525.

Bonow RO, Berman DS, Gibbons RJ, et al. Special report. Cardiac positron emission tomography. A report for health professionals from the committee on advanced cardiac imaging and technology of the Council on Clinical Cardiology, American Heart Association. Circulation 1991; 84(1): 447-454.

Doyle WK, Budinger TF, Valk PE, et al. Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography. J Comput Assist Tomogr 1987; 11(4): 563-570.

Hawkins RA, Phelps ME. PET in clinical oncology. Cancer Metastasis Rev 1988; 7(2): 119-142.

Joensu H, Ahonen A. Imaging of metastases of thyroid carcinoma with fluorine-18 fluorodeoxyglucose. J Nucl Med 1987; 28: 910-914.

Maisey MN, Britton KE, Gilday DL. Clinical Nuclear Medicine. 2nd ed. Philadelphia: J.B. Lippincott; 1991; 31.

Reivich M, Kuhl D, Wolf A, et al. The [ 18F] fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 1979; 44(1): 127-137.

Schelbert HR, et al. Assessment of regional myocardial ischemia by positron-emission computed tomography. Am Heart J 1982; 103:588.

Schwaiger M, Hicks R. The clinical role of metabolic imaging of the heart by positron emission tomography. J Nucl Med 1991; 32: 565-578.

Yonekura Y, et al. Increased accumulation of 2-deoxy-2-[ 18F]fluoro-D-glucose in liver metastases from colon carcinoma. J Nucl Med 1982; 23: 1133-1137.

[18F]-Sodium Fluoride (18F-NaF)


Sodium Fluoride F 18 Injection is a radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging of bone to define areas of altered osteogenic activity. The agent is a highly sensitive bone-seeking PET tracer used for detection of skeletal abnormalities (NIH 2008). The uptake mechanism of [18F]-Sodium Fluoride resembles that of [99mTc]-MDP with better pharmacokinetic characteristics including faster blood clearance and two-fold higher uptake in bone. Uptake of [18F]-Sodium Fluoride reflects blood flow and bone remodeling. The use of novel hybrid PET/CT systems, has significantly improved the specificity of [18F]-Sodium Fluoride imaging as the CT component of the study allows morphologic characterization of the functional lesion and more accurate differentiation between benign lesions and metastases.


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15O-Water Chemical Structural Formula

H215O ([O-15] Water) is a radiolabeled imaging agent that has been used for investigating tumor blood flow and perfusion. There is also a long history of using H215O in brain mapping studies prior to fMRI. In addition, H215O has been used to assess brain blood flow and perfusion and cardiac blood flow and perfusion.

The mechanism of action of H215O is based on the distribution and clearance of water from the tissues [Huang 1983]. H215O is an inert tracer [Stocklin 1993, Huang 1983]. It is freely diffusible (approximately 95% extraction fraction in primates under normal blood flow conditions) across the blood-brain barrier; thus, the delivered tracer can diffuse quickly into the extravascular space [Huang 1983]. Due to the small size of the water molecule, the distribution of H215O in the brain reflects the tissue perfusion at the capillary level. Since H215O is not chemically trapped in tissue, it will be cleared gradually from the tissue by blood flow; the larger the blood flow, the faster the clearance occurs [Huang 1983].The rate of clearance can be directly correlated to perfusion of the tissue of interest.


Huang SC, Carson RE, Hoffman EJ, et al. Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and 15O-water. J Cereb Blood Flow Metab 3(2): 141-153, 1983.

Stöcklin G, Pike VW, editors. Radiopharmaceuticals for positron emission tomography: methodological aspects. Boston: Kluwer Academic Publishers p. 2, 12-3, 121, 127-128, 1993.


11C-Acetate Chemical Structural Formula

[11C]-Acetate is a radiolabeled imaging agent that has been used for investigating tumor lipid membrane synthesis and myocardial metabolism. [11C]-Acetate is a metabolic substrate of beta-oxidation and a precursor of amino acids, fatty acids, and sterol. In vitro studies suggest that high tumor-to-normal ratios of [11C]-Acetate are mainly due to enhanced lipid synthesis reflecting the growth activity of neoplasms [Yoshimoto 2001]. [11C]-Acetate PET has received significant interest for detecting and staging prostate cancer and other malignancies. Initial studies also show promise in characterizing tumors of the brain, lung (NSCLC), liver, lymphoma, nasopharyngeal carcinoma, ovarian cancer, and colon cancer. [11C]-Acetate generally experiences rapid and high uptake, with rapid washout from normal tissues but slower washout (or retention) in malignant tumors [Kato 2002, Yeh 1999, Higashi 2004].


Higashi K, Ueda Y, Matsunari I, Kodama Y, Ikeda R, Miura K, Taki S, Higuchi T, Tonami H, Yamamoto I. 11C-acetate PET imaging of lung cancer: comparison with 18F-FDG PET and 99mTc-MIBI SPET. Eur J Nucl Med Mol Imaging. 2004; 31:13-21

Kato T, Tsukamoto E, Kuge Y, Takei T, Shiga T, Shinohara N, Katoh C, Nakada K, Tamaki N. Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer. Eur J Nucl Med Mol Imaging. 2002; 29:1492-1495

Yeh SH, Liu RS, Wu LC, Yen SH, Chang CW, Chen KY: 11C-acetate clearance in nasopharyngeal carcinoma. Nucl Med Commun. 1999; 20:131-134

Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, Takahashi N, Welch MJ, Fujibayashi Y: Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells. Nucl Med Biol. 2001; 28:117-122

3’-deoxy-3’-[18F]-Fluorothymide (FLT)

3'-deoxy-3'-18F-Flurothymide (FLT) Chemical Structural Formula

3'-deoxy-3'-[18F]-Fluorothymidine (FLT) is a structural analog of the DNA constituent, thymidine. It is a radiolabeled imaging agent that has been proposed for investigating cellular proliferation with positron emission tomography (PET).

Although FLT is not incorporated into DNA, it is trapped in the cell, due to phosphorylation by thymidine kinase, a part of the proliferation pathway. As such it has the potential to image proliferating tumor cells in proportion to the DNA synthesis rate. Therefore 3'-deoxy-3'-[F-18]fluorothymidine [F-18] FLT is a PET agent that can be used to image proliferation in malignant cells and monitor response to therapies known to effect proliferation [Shields 1998, Vesselle 2002].


Shields AF, Grierson JR, Dohmen B M, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, Obradovich J, Muzik O, and Mangner T. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med; 4:1334–1336, 1998

Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, Peterson LM, Vallieres E, Wood DE. In Vivo Validation of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) as a Proliferation Imaging Tracer in Humans: Correlation of [18F]FLT Uptake by Positron Emission Tomography with Ki-67 Immunohistochemistry and Flow Cytometry in Human Lung Tumors. Clinical Cancer Research; 8:3315–3323, 2002

[11C]-6-HO-BTA-1 ([11C]-PIB)

11C-6-HO-BTA-1 (11C-PIB) Chemical Structural Formula

[C11]-PIB otherwise known as (N-methyl-[11C])6-OH-BTA-1 is a thioflavin-T derivative that binds to amyloid-beta (Aβ) peptide fibrils associated with Alzheimer’s disease. This compound is one of the early stage imaging agents utilized to measure amyloid load in humans. Amyloid plaques are believed to play an integral role in Alzheimer’s disease and therefore could be used to correlate cognitive decline [Klunk 2003, Klunk 2004].


Klunk WE, Wang Y, Huang GF, et al. The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 23:2086–2092, 2003.

Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55(3):306-319, 2004.

[18F]-Fluoromisonidazole (FMISO)

18-F-Fluoromisonidazaole (FMISO) Chemical Structural Formula

1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole or [18F]-FMISO is a radiolabeled imaging agent that has been used for investigating tumor hypoxia with positron emission tomography (PET) [Graham 1997, Silverman 1998, Rofstad 1999]. [18F]FMISO is an azomycin-based hypoxic cell sensitizer that has a nearly ideal partition coefficient and, when reduced by hypoxia, binds covalently to cellular molecules at rates that are inversely proportional to intracellular oxygen concentration, rather than by any downstream biochemical interactions.


Graham MM, Peterson LM, Link JM, et al. Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. J Nucl Med 1997;38:1631-6.

Rofstad EK and Danielsen T. Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis. Br J Cancer 1999;80:1697-707.

Silverman DH, Hoh CK, Seltzer MA, et al. Evaluating tumor biology and oncological disease with positron-emission tomography. Semin Radiat Oncol 1998;8:183-96.


18F-Flutemetamol Chemical Structural Formula

[18F]-Flutemetamol or 18F-39-F-6-OH-BTA1 is a fluorine-18 labelled PET diagnostic agent for measuring Aβ plaques and behave very similar to 11C-PIB but has the advantage of the 120-minute half-life of [18F] compared to 20 minutes for [11C] [Koole 2009, Nelissen 2009]. It is derived from the basic structure of the dye thioflavin-T and can be used as an aid in diagnosis of Alzheimer’s disease.


Koole M, Lewis DM, Buckley et al. Whole-Body Biodistribution and Radiation Dosimetry of 18F-GE067: A Radioligand for In Vivo Brain Amyloid Imaging. J Nucl Med 2009; 50:818–822.

Nelissen N, Van Laere K, Thurfjell L et al. Phase 1 study of the Pittsburgh compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med. 2009;50(8):1251-9.

[18F] Fluciclovine

18F Fluciclovine Chemical Structural Formula

[18F] Fluciclovine is a synthetic L-leucine analogue that is actively transported into mammalian cells by amino acid transporters (AAT). The radiopharmaceutical is unique as it is not incorporated into newly synthesized proteins. Following injection, [18F] Fluciclovine is preferentially taken up into cells with enhanced amino acid transport, such as tumor cells that require increased amounts of amino acids to support increased metabolism and proliferation.


Shoup TM, Goodman MM. Synthesis of [F-18]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC): A PET tracer for tumor delineation. Journal of Labelled Compounds & Radiopharmaceuticals. 1999;42:215-225.

Shoup TM, Olson J, Hoffman JM, et al. Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxilic acid to image brain tumors. J Nucl Med. 1999;Feb;40(2):331-338.

Schuster DM, Nye JA, Nieh PT, et al. Initial experience with the radiotracer anti-1-amino-3-[18F]Fluorocyclobutane-1-carboxylic acid (anti-[ 18F]FACBC) with PET in renal carcinoma. Mol Imaging Biol. 2009;11(6):434-438