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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2015

01-11-2015 | Original Article

Biodistribution of the 18F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

Authors: Ryogo Minamimoto, Mehran Jamali, Amir Barkhodari, Camila Mosci, Erik Mittra, Bin Shen, Frederick Chin, Sanjiv Sam Gambhir, Andrei Iagaru

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2015

Login to get access

Abstract

Purpose

The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (18F-FPPRGD2) in cancer patients and to compare its uptake in malignant lesions with 18F-FDG uptake.

Methods

A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had 18F-FPPRGD2 PET/CT prior to treatment. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between 18F-FPPRGD2 uptake and 18F-FDG uptake were also evaluated in 28 of the 35 patients.

Results

Areas of high 18F-FPPRGD2 accumulation (SUVmax range 8.9 – 94.4, SUVmean range 7.1 – 64.4) included the bladder and kidneys. Moderate uptake (SUVmax range 2.1 – 6.3, SUVmean range 1.1 – 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with 18F-FDG, 18F-FPPRGD2 showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUVmax and SUVmean) for 18F FPPRGD2 and those for 18F-FDG.

Conclusion

The biodistribution of 18F-FPPRGD2 in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between 18F-FPPRGD2 and 18F-FDG uptake confirms that the information provided by each PET tracer is different.
Literature
1.
2.
3.
4.
Jimenez B, Volpert OV. Mechanistic insights on the inhibition of tumor angiogenesis. J Mol Med. 2001;78:663–72.CrossRefPubMed
5.
Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer. 2004;100:2491–9.CrossRefPubMed
6.
Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.CrossRefPubMed
7.
8.
Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994;264:569–71.CrossRefPubMed
9.
Max R, Gerritsen RR, Nooijen PT, Goodman SL, Sutter A, Keilholz U, et al. Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas. Int J Cancer. 1997;71:320–4.CrossRefPubMed
10.
Wu WB, Peng HC, Huang TF. Disintegrin causes proteolysis of beta-catenin and apoptosis of endothelial cells. Involvement of cell-cell and cell-ECM interactions in regulating cell viability. Exp Cell Res. 2003;286:115–27.CrossRefPubMed
11.
Okada Y, Copeland BR, Hamann GF, Koziol JA, Cheresh DA, Del Zoppo GJ. Integrin alphavbeta3 is expressed in selected microvessels after focal cerebral ischemia. Am J Pathol. 1996;149:37–44.PubMedCentralPubMed
12.
Eliceiri BP, Cheresh DA. Role of alpha v integrins during angiogenesis. Cancer J. 2000;6 Suppl 3:S245–9.PubMed
13.
Felding-Habermann B, O’Toole TE, Smith JW, Fransvea E, Ruggeri ZM, Ginsberg MH, et al. Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A. 2001;98:1853–8.PubMedCentralCrossRefPubMed
14.
Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994;79:1157–64.CrossRefPubMed
15.
Shannon KE, Keene JL, Settle SL, Duffin TD, Nickols MA, Westlin M, et al. Anti-metastatic properties of RGD-peptidomimetic agents S137 and S247. Clin Exp Metastasis. 2004;21:129–38.CrossRefPubMed
16.
Haubner R, Wester HJ. Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies. Curr Pharm Des. 2004;10:1439–55.CrossRefPubMed
17.
Cai W, Chen X. Multimodality molecular imaging of tumor angiogenesis. J Nucl Med. 2008;49 Suppl 2:113S–28S.CrossRefPubMed
18.
Chen X. Multimodality imaging of tumor integrin alphavbeta3 expression. Mini Rev Med Chem. 2006;6:227–37.CrossRefPubMed
19.
Beer AJ, Haubner R, Goebel M, Luderschmidt S, Spilker ME, Wester HJ, et al. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl Med. 2005;46:1333–41.PubMed
20.
Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res. 2006;12:3942–9.CrossRefPubMed
21.
Beer AJ, Niemeyer M, Carlsen J, Sarbia M, Nährig J, Watzlowik P, et al. Patterns of alphavbeta3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J Nucl Med. 2008;49:255–9.CrossRefPubMed
22.
Beer AJ, Lorenzen S, Metz S, Herrmann K, Watzlowik P, Wester HJ, et al. Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG. J Nucl Med. 2008;49:22–9.CrossRefPubMed
23.
Haubner R, Weber WA, Beer AJ, Vabuliene E, Reim D, Sarbia M, et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med. 2005;2:e70.PubMedCentralCrossRefPubMed
24.
McParland BJ, Miller MP, Spinks TJ, Kenny LM, Osman S, Khela MK, et al. The biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 18F-AH111585 in healthy volunteers. J Nucl Med. 2008;49:1664–7.CrossRefPubMed
25.
Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med. 2008;49:879–86.CrossRefPubMed
26.
Boturyn D, Coll JL, Garanger E, Favrot MC, Dumy P. Template assembled cyclopeptides as multimeric system for integrin targeting and endocytosis. J Am Chem Soc. 2004;126:5730–9.CrossRefPubMed
27.
Liu S, Liu Z, Chen K, Yan Y, Watzlowik P, Wester HJ, et al. 18F-labeled galacto and PEGylated RGD dimers for PET imaging of αvβ3 integrin expression. Mol Imaging Biol. 2010;12:530–8.PubMedCentralCrossRefPubMed
28.
Mittra ES, Goris ML, Iagaru AH, Kardan A, Burton L, Berganos R, et al. Pilot pharmacokinetic and dosimetric studies of (18)F-FPPRGD2: a PET radiopharmaceutical agent for imaging α(v)β(3) integrin levels. Radiology. 2011;260:182–91.PubMedCentralCrossRefPubMed
29.
Iagaru A, Mosci C, Shen B, Chin FT, Mittra E, Telli ML, et al. 18F-FPPRGD2 PET/CT: pilot phase evaluation of breast cancer patients. Radiology. 2014;273:549–59.CrossRefPubMed
30.
Iagaru A, Mosci C, Jamali M, Minamimoto R, Mittra E, Shen B, et al. 18F FPPRGD2 PET/CT evaluation of patients with suspected recurrence of glioblastoma multiforme (abstract no. 31). J Nucl Med. 2014;55 Suppl 1:31.
31.
Chin FT, Shen B, Liu S, Berganos RA, Chang E, Mittra E, et al. First experience with clinical-grade ([18F]FPP(RGD2): an automated multi-step radiosynthesis for clinical PET studies. Mol Imaging Biol. 2012;14:88–95.PubMedCentralCrossRefPubMed
32.
Delbeke D, Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med. 2006;47:885–95.PubMed
33.
Wu Z, Li ZB, Cai W, He L, Chin FT, Li F, et al. 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of alphavbeta3 integrin expression. Eur J Nucl Med Mol Imaging. 2007;34:1823–31.PubMedCentralCrossRefPubMed
34.
Zhang X, Xiong Z, Wu Y, Cai W, Tseng JR, Gambhir SS, et al. Quantitative PET imaging of tumor integrin alphavbeta3 expression with 18F-FRGD2. J Nucl Med. 2006;47:113–21.PubMedCentralPubMed
35.
Li ZB, Chen K, Chen X. (68)Ga-labeled multimeric RGD peptides for microPET imaging of integrin alpha(v)beta (3) expression. Eur J Nucl Med Mol Imaging. 2008;35:1100–8.CrossRefPubMed
36.
Li ZB, Cai W, Cao Q, Chen K, Wu Z, He L, et al. (64)Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression. J Nucl Med. 2007;48:1162–71.CrossRefPubMed
37.
Guo N, Lang L, Gao H, Niu G, Kiesewetter DO, Xie Q, et al. Quantitative analysis and parametric imaging of 18F-labeled monomeric and dimeric RGD peptides using compartment model. Mol Imaging Biol. 2012;14:743–52.PubMedCentralCrossRefPubMed
38.
Paulus W, Baur I, Schuppan D, Roggendorf W. Characterization of integrin receptors in normal and neoplastic human brain. Am J Pathol. 1993;143:154–63.PubMedCentralPubMed
39.
Singh B, Fu C, Bhattacharya J. Vascular expression of the alpha(v)beta(3)-integrin in lung and other organs. Am J Physiol Lung Cell Mol Physiol. 2000;278:L217–26.PubMed
40.
Terracio L, Rubin K, Gullberg D, Balog E, Carver W, Jyring R, et al. Expression of collagen binding integrins during cardiac development and hypertrophy. Circ Res. 1991;68:734–44.CrossRefPubMed
41.
Maitra N, Flink IL, Bahl JJ, Morkin E. Expression of a and b integrins during terminal differentiation of cardiomyocytes. Cardiovasc Res. 2000;47:715–25.CrossRefPubMed
42.
Hughes DE, Salter DM, Dedhar S, Simpson R. Integrin expression in human bone. J Bone Miner Res. 1993;8:527–33.CrossRefPubMed
43.
Annikki Liakka K. The integrin subunits α2, α3, α4, α5, α6, αV, β1 and β3 in fetal, infant and adult human spleen as detected by immunohistochemistry. Differentiation. 1994;56:183–90.CrossRef
44.
Haubner R, Wester HJ, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001;42:326–36.PubMed
45.
Kim JH, Lee JS, Kang KW, Lee HY, Han SW, Kim TY, et al. Whole-body distribution and radiation dosimetry of (68)Ga-NOTA-RGD, a positron emission tomography agent for angiogenesis imaging. Cancer Biother Radiopharm. 2012;27:65–71.CrossRefPubMed
46.
Doss M, Kolb HC, Zhang JJ, Bélanger MJ, Stubbs JB, Stabin MG, et al. Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans. J Nucl Med. 2012;53:787–95.CrossRefPubMed
47.
Cirulli V, Beattie GM, Klier G, Ellisman M, Ricordi C, Quaranta V, et al. Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells. J Cell Biol. 2000;150:1445–60.PubMedCentralCrossRefPubMed
48.
Liu Z, Liu S, Wang F, Liu S, Chen X. Noninvasive imaging of tumor integrin expression using (18)F-labeled RGD dimer peptide with PEG (4) linkers. Eur J Nucl Med Mol Imaging. 2009;36:1296–307.CrossRefPubMed
49.
Giatromanolaki A, Koukourakis MI, Theodossiou D, et al. Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer. Clin Cancer Res. 1997;3:2485–92.PubMed
50.
Lorger M, Krueger JS, O’Neal M, et al. Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A. 2009;106:10666–71.PubMedCentralCrossRefPubMed
51.
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 in tumor vascularity after antitumor therapy. J Nucl Med. 2009;50:116–22.CrossRefPubMed
52.
Dumont RA, Hildebrandt I, Su H, et al. Noninvasive imaging of {alpha}V{beta}3 function as a predictor of the antimigratory and antiproliferative effects of dasatinib. Cancer Res. 2009;69:3173–9.PubMedCentralCrossRefPubMed
53.
Sun X, Yan Y, Liu S, et al. 18F-FPPRGD2 and 18F-FDG PET of response to Abraxane therapy. J Nucl Med. 2011;52:140–6.CrossRefPubMed
Metadata
Title
Biodistribution of the 18F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements
Authors
Ryogo Minamimoto
Mehran Jamali
Amir Barkhodari
Camila Mosci
Erik Mittra
Bin Shen
Frederick Chin
Sanjiv Sam Gambhir
Andrei Iagaru
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2015
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-015-3096-4

Other articles of this Issue 12/2015

European Journal of Nuclear Medicine and Molecular Imaging 12/2015 Go to the issue

Original Article

Pseudarthrosis after lumbar spinal fusion: the role of 18F-fluoride PET/CT

Original Article

Feasibility of one-eighth time gated myocardial perfusion SPECT functional imaging using IQ-SPECT

Original Article

Repeatability of hypoxia PET imaging using [18F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Editorial

Prostate cancer recurrence: can PSA guide imaging?

Original Article

Basal 18 F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

Original Article

18F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data