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
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 4/2015

Open Access 01-05-2015 | Original Article

High-uptake areas on positron emission tomography with the hypoxic radiotracer 18F-FRP170 in glioblastomas include regions retaining proliferative activity under hypoxia

Authors: Takaaki Beppu, Toshiaki Sasaki, Kazunori Terasaki, Hiroaki Saura, Hideki Mtsuura, Kuniaki Ogasawara, Makoto Sasaki, Shigeru Ehara, Ren Iwata, Yoshihiro Takai

Published in: Annals of Nuclear Medicine | Issue 4/2015

Login to get access

Abstract

Objective

The aim was to evaluate the proliferative activity of high-uptake areas on positron emission tomography (PET) with the hypoxic cell radiotracer, 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170).

Methods

Thirteen patients with glioblastoma underwent FRP170 PET before tumor resection. During surgery, tumor specimens were stereotaxically obtained from regions corresponding to high (high-uptake areas, HUAs) and relatively low (low-uptake areas, LUAs) accumulation of FRP170. We compared immunohistochemical staining for Ki-67 and hypoxia-inducible factor (HIF)-1α between HUA and LUA.

Results

HIF-1α index was significantly higher in HUAs than in LUAs. In contrast, mean Ki-67 indices did not differ significantly between HUAs and LUAs.

Conclusions

Findings for HIF-1α index clearly indicated that HUAs on FRP170 PET represented hypoxic regions in glioblastoma. However, findings of Ki-67 index suggest that HUAs on FRP170 PET include regions retaining proliferative activity regardless of tissue hypoxia.
Literature
1.
Jensen RL. Hypoxia in the tumorigenesis of gliomas and as a potential target for therapeutic measures. Neurosurg Focus. 2006;20(4):E24.CrossRefPubMed
2.
3.
4.
Beppu T, Terasaki K, Sasaki T, Fujiwara S, Matsuura H, Ogasawara K, et al. Standardized uptake value in high uptake area on positron emission tomography with 18F-FRP170 as a hypoxic cell tracer correlates with intratumoral oxygen pressure in glioblastoma. Mol Imag Biol. 2014;16:127–35.CrossRef
5.
Ishikawa Y, Iwata R, Furumoto S, Takai Y. Automated preparation of hypoxic cell marker [18F]FRP-170 by on-column hydrolysis. Appl Radiat Isot. 2005;62(5):705–10.CrossRefPubMed
6.
Kaneta T, Takai Y, Iwata R, Hakamatsuka T, Yasuda H, Nakayama K, et al. Initial evaluation of dynamic human imaging using 18F-FRP170 as a new PET tracer for imaging hypoxia. Ann Nucl Med. 2007;21(2):101–7.CrossRefPubMed
7.
Kaneta T, Takai Y, Kagaya Y, Yamane Y, Wada H, Yuki M, et al. Imaging of ischemic but viable myocardium using a new 18F-labeled 2-nitroimidazole analog, 18F-FRP170. J Nucl Med. 2002;43(1):109–16.PubMed
8.
Shibahara I, Kumabe T, Kanamori M, Saito R, Sonoda Y, Watanabe M, et al. Imaging of hypoxic lesions in patients with gliomas by using positron emission tomography with 1-(2-[18F] fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, a new 18F-labeled 2-nitroimidazole analog. J Neurosurg. 2010;113(2):358–68.CrossRefPubMed
9.
Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, et al. Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med. 2005;46(2):253–60.PubMed
10.
Kawai N, Maeda Y, Kudomi N, Miyake K, Okada M, Yamamoto Y, et al. Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma. Eur J Nucl Med Mol Imaging. 2011;38(3):441–50.CrossRefPubMed
11.
Swanson KR, Chakraborty G, Wang CH, Rockne R, Harpold HL, Muzi M, et al. Complementary but distinct roles for MRI and 18F-fluoromisonidazole PET in the assessment of human glioblastomas. J Nucl Med. 2009;50(1):36–44.CrossRefPubMedCentralPubMed
12.
Narita T, Aoyama H, Hirata K, Onodera S, Shiga T, Kobayashi H, et al. Reoxygenation of glioblastoma multiforme treated with fractionated radiotherapy concomitant with temozolomide: changes defined by 18F-fluoromisonidazole positron emission tomography: two case reports. Jpn J Clin Oncol. 2012;42(2):120–3.CrossRefPubMed
13.
Heijmen L, Ter Voert EG, Punt CJ, Heerschap A, Oyen WJ, Bussink J, et al. Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model. Contrast Media Mol Imaging. 2014;9(3):237–45.CrossRefPubMed
14.
Tanaka T, Furukawa T, Fujieda S, Kasamatsu S, Yonekura Y, Fujibayashi Y. Double-tracer autoradiography with Cu-ATSM/FDG and immunohistochemical interpretation in four different mouse implanted tumor models. Nucl Med Biol. 2006;33(6):743–50.CrossRefPubMed
15.
Dence CS, Ponde DE, Welch MJ, Lewis JS. Autoradiographic and small-animal PET comparisons between (18)F-FMISO, (18)F-FDG, (18)F-FLT and the hypoxic selective (64)Cu-ATSM in a rodent model of cancer. Nucl Med Biol. 2008;35(6):713–20.CrossRefPubMedCentralPubMed
16.
Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU, et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res. 2004;10(7):2245–52.CrossRefPubMed
17.
Hatano T, Zhao S, Zhao Y, Nishijima K, Kuno N, Hanzawa H, et al. Biological characteristics of intratumoral [F-18]fluoromisonidazole distribution in a rodent model of glioma. Int J Oncol. 2013;42(3):823–30.PubMedCentralPubMed
18.
Cherk MH, Foo SS, Poon AM, Knight SR, Murone C, Papenfuss AT, et al. Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET. J Nucl Med. 2006;47(12):1921–6.PubMed
19.
Evans SM, Jenkins KW, Chen HI, Jenkins WT, Judy KD, Hwang WT, et al. The relationship among hypoxia, proliferation, and outcome in patients with de novo glioblastoma: a pilot study. Transl Oncol. 2010;3(3):160–9.CrossRefPubMedCentralPubMed
20.
Chapman JD. Hypoxic sensitizers–implications for radiation therapy. New Engl J Med. 1979;301(26):1429–32.CrossRefPubMed
21.
Krohn KA, Link JM, Mason RP. Molecular imaging of hypoxia. J Nucl Med. 2008;49(Suppl 2):129S–48S.CrossRefPubMed
22.
Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270(3):1230–7.CrossRefPubMed
23.
Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D. Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathol. 2005;15(4):297–310.CrossRefPubMed
24.
Denekamp J, Dasu A. Inducible repair and the two forms of tumour hypoxia–time for a paradigm shift. Acta Oncol. 1999;38(7):903–18.CrossRefPubMed
25.
Raleigh JA, Zeman EM, Calkins DP, McEntee MC, Thrall DE. Distribution of hypoxia and proliferation associated markers in spontaneous canine tumors. Acta Oncol. 1995;34(3):345–9.CrossRefPubMed
26.
Ljungkvist AS, Bussink J, Rijken PF, Kaanders JH, van der Kogel AJ, Denekamp J. Vascular architecture, hypoxia, and proliferation in first-generation xenografts of human head-and-neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2002;54(1):215–28.CrossRefPubMed
27.
Evans SM, Hahn SM, Magarelli DP, Koch CJ. Hypoxic heterogeneity in human tumors: eF5 binding, vasculature, necrosis, and proliferation. Am J Clin Oncol. 2001;24(5):467–72.CrossRefPubMed
28.
Hoogsteen IJ, Marres HA, Wijffels KI, Rijken PF, Peters JP, van den Hoogen FJ, et al. Colocalization of carbonic anhydrase 9 expression and cell proliferation in human head and neck squamous cell carcinoma. Clin Cancer Res. 2005;11(1):97–106.PubMed
29.
Evans SM, Jenkins KW, Jenkins WT, Dilling T, Judy KD, Schrlau A, et al. Imaging and analytical methods as applied to the evaluation of vasculature and hypoxia in human brain tumors. Radiat Res. 2008;170(6):677–90.CrossRefPubMedCentralPubMed
30.
Rasey JS, Hofstrand PD, Chin LK, Tewson TJ. Characterization of [18F]fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia. J Nucl Med. 1999;40(6):1072–9.PubMed
31.
32.
Schmaltz C, Hardenbergh PH, Wells A, Fisher DE. Regulation of proliferation-survival decisions during tumor cell hypoxia. Mol Cell Biol. 1998;18(5):2845–54.PubMedCentralPubMed
33.
Webster L, Hodgkiss RJ, Wilson GD. Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo. Br J Cancer. 1998;77(2):227–34.CrossRefPubMedCentralPubMed
Metadata
Title
High-uptake areas on positron emission tomography with the hypoxic radiotracer 18F-FRP170 in glioblastomas include regions retaining proliferative activity under hypoxia
Authors
Takaaki Beppu
Toshiaki Sasaki
Kazunori Terasaki
Hiroaki Saura
Hideki Mtsuura
Kuniaki Ogasawara
Makoto Sasaki
Shigeru Ehara
Ren Iwata
Yoshihiro Takai
Publication date
01-05-2015
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 4/2015
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-015-0951-0

Other articles of this Issue 4/2015

Annals of Nuclear Medicine 4/2015 Go to the issue

Original Article

Positron emission tomography-based evidence of low-amplitude respiratory motion in patients with chronic obstructive pulmonary disease

Original Article

Comparison of glomerular filtration rate measurements with two plasma and single plasma sample methods in renal transplant cases with stable renal graft functions

Original Article

Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [11C]CB184 and [11C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [11C](R)-PK11195

Technical Note

Effects of filtration on right ventricular function by the gated blood pool SPECT

Original Article

A myocardial perfusion imaging system using a multifocal collimator for detecting coronary artery disease: validation with invasive coronary angiography

Case Report

Parathyroid adenoma upstaging the lung cancer