Current Radiopharmaceutical Availability
2-deoxy-2-[18F]fluoro-D-glucose (FDG) which 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 positron emission tomography (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 positron emission tomography (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].
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]-Fluoride is a highly sensitive bone-seeking PET tracer used for detection of skeletal abnormalities (NIH 2008). The uptake mechanism of 18F-Fluoride resembles that of [99mTc]-MDP with better pharmacokinetic characteristics including faster blood clearance and two-fold higher uptake in bone. Uptake of [18F]-Fluoride reflects blood flow and bone remodeling. The use of novel hybrid PET/CT systems, has significantly improved the specificity of 18F- 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.
Sodium fluoride F 18 injection investigator’s brochure. Release Date: August 2008. Cancer Imaging Program Division of Cancer Treatment and Diagnosis National Institutes of Health. Available at: http://imaging.cancer.gov/images/Documents/bccff836-d508-4ceb-b22a-894f563cc352/NaF_IB_Edition1_072808..pdf.
H215O ([O-15] Water) which 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 which 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]-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
[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.
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 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] Fluciclatide Injection is a fluorine-18 labelled synthetic cyclic peptide coupled to a PEG side chain which carries a fluorophenyl group that is radiolabelled with fluorine-18. The peptide contains the tripeptide Arg-Gly-Asp (RGD) motif present in a configuration that allows it to bind to certain integrin receptors, such as αvβ3 and αvβ5 that are associated with angiogenesis and are upregulated on endothelial cells during angiogenesis. These integrin receptors are associated with endothelial cell differentiation, proliferation, migration and attachment to the extracellular matrix. Targeting receptors that are upregulated or selectively expressed on endothelial cells in areas undergoing angiogenesis is a validated approach to the treatment of cancer and other diseases that are associated with angiogenesis, In the adult healthy body, angiogenesis is well controlled, only occurring during events such as the menstrual cycle, reproduction and wound healing. Fluciclatide is a new chemical entity that has demonstrated high nanomolar affinity for the αvβ3 receptor when radiolabelled with fluorine-18 and using Positron Emission Tomography (PET) [Kenney 2008, McParland 2008, Morrison 2009].
Kenny LM, Coombes RC, Oulie I, Contracto KB, Miller M, Spinks TJ, McParland B, Cohen PS, Hui AM, Palmieri C, Osman S, Glaser M, Turton D, Al-Nahhas A, Aboagye EO. Phase I trial of the Positron-Emitting Arg-Gly-Asp (RGD) Peptide Radioligand 18F-AH111585 in Breast Cancer Patients. J Nucl Med 2008; 49:879-886
McParland BJ, Miller MP, Spinks TJ, Kenny LM, Osman S, Khela MK, Aboagye E, Coombes RC, Hui AM, Cohen PS. The Biodistribution and radiation dosimetry of the Arg-Gly-Asp Peptide 18F-AH111585 in healthy volunteers. J Nucl Med 2008; 49:1664-1667
Morrison MS, Ricketts SA, Barnett J, Cuthbertson A, Tessier J, Wedge SR. Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes intumor vascularity after antitumor therapy. J Nucl Med. 2009;50(1):116-22