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01-07-2012 | Molecular Imaging

Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

Authors: Eric O. Aboagye, Fiona J. Gilbert, Ian N. Fleming, Ambros J. Beer, Vincent J. Cunningham, Paul K. Marsden, Dimitris Visvikis, Antony D. Gee, Ashley M. Groves, Laura M. Kenny, Gary J. Cook, Paul E. Kinahan, Melvyn Myers, Larry Clarke

Published in: European Radiology | Issue 7/2012

Abstract

The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [¹⁵O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics.

Key Points

• [ ¹⁵ O]-water is the gold standard for blood flow/tissue perfusion with PET

• In some instances dynamic [ ¹⁸ F]-FDG uptake may be used to estimate perfusion

• Radiopharmaceuticals that target integrins are now being evaluated for measuring tumour vascularity

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Workman P, Aboagye EO, Chung Y et al (2006) Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. J Natl Cancer Inst 98:580–598PubMedCrossRef

Lammertsma AA, Frackowiak RSJ, Hoffman JM et al (1989) The C15O2 build-up technique to measure regional cerebral blood flow and volume of distribution of water. J Cereb Blood Flow Metab 9:461–470PubMedCrossRef

Hoekstra CJ, Stroobants SG, Hoekstra OS, Smit EF, Vansteenkiste JF, Lammertsma AA (2002) Measurement of perfusion in stage IIIA-N2 non-small cell lung cancer using H2 15O and positron emission tomography. Clin Cancer Res 8:2109–2115PubMed

Iida H, Rhodes CG, De Silva R et al (1992) Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. J Nucl Med 33:1669–1677PubMed

De Langen AJ, Van Den Boogaart VEM, Marcus JT, Lubberink M (2008) Use of H2 15O-PET and DCE-MRI to measure tumor blood flow. Oncologist 13:631–644PubMedCrossRef

Wilson CBJH, Lammertsma AA, McKenzie CG, Sikora K, Jones T (1992) Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: A rapid and noninvasive dynamic method. Cancer Res 52:1592–1597PubMed

Wells P, Jones T, Price P (2003) Assessment of inter- and intrapatient variability in C15O 2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers. Clin Cancer Res 9:6350–6356PubMed

De Langen AJ, Lubberink M, Boellaard R et al (2008) Reproducibility of tumor perfusion measurements using15O-labeled water and PET. J Nucl Med 49:1763–1768PubMedCrossRef

Lodge MA, Jacene HA, Pili R, Wahl RL (2008) Reproducibility of tumor blood flow quantification with15O-water PET. J Nucl Med 49:1620–1627PubMedCrossRef

10.

Burke D, Davies MM, Zweit J et al (2001) Continuous angiotensin II infusion increases tumour: Normal blood flow ratio in colo-rectal liver metastases. Br J Cancer 85:1640–1645PubMedCrossRef

11.

Taniguchi H, Koyama H, Masuyama M et al (1996) Angiotensin-II-induced hypertension chemotherapy: Evaluation of hepatic blood flow with oxygen-15 PET. J Nucl Med 37:1522–1523PubMed

12.

Koh T, Taniguchi H, Yamagishi H (2003) Oxygen-15 positron-emission tomography for predicting selective delivery of a chemotherapeutic agent to hepatic cancers during angiotensin II-induced hypertension. Cancer Chemother Pharmacol 51:349–358PubMed

13.

Anderson HL, Yap JT, Miller MP, Robbins A, Jones T, Price PM (2003) Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate. J Clin Oncol 21:2823–2830PubMedCrossRef

14.

Logan TF, Jadali F, Egorin MJ et al (2002) Decreased tumor blood flow as measured by positron emission tomography in cancer patients treated with interleukin-1 and carboplatin on a phase I trial. Cancer Chemother Pharmacol 50:433–444PubMedCrossRef

15.

Kötz B, West C, Saleem A, Jones T, Price P (2009) Blood flow and vd (water): Both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue. Mol Cancer Ther 8:303–309PubMedCrossRef

16.

Herbst RS, Mullani NA, Davis DW et al (2002) Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. J Clin Oncol 20:3804–3814PubMedCrossRef

17.

Anderson H, Yap JT, Wells P et al (2003) Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane. Br J Cancer 89:262–267PubMedCrossRef

18.

Saleem A, Yap J, Osman S et al (2000) Modulation of fluorouracil tissue pharmacokinetics by eniluracil: In-vivo imaging of drug action. Lancet 355:2125–2131PubMedCrossRef

19.

Harte RJA, Matthews JC, O'Reilly SM et al (1999) Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa. J Clin Oncol 17:1580–1589PubMed

20.

Gupta N, Saleem A, Kötz B et al (2006) Carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients. Clin Cancer Res 12:3115–3123PubMedCrossRef

21.

Kurdziel KA, Figg WD, Carrasquillo JA et al (2003) Using positron emission tomography 2-deoxy-2-[18F]fluoro-D-glucose, 11CO, and 15O-water for monitoring androgen independent prostate cancer. Mol Imaging Biol 5:86–93PubMedCrossRef

22.

Luurtsema G, Boellaard R, Greuter HNJM et al (2010) Pharmaceutical preparation of oxygen-15 labelled molecular oxygen and carbon monoxide gasses in a hospital setting. J Clin Pharm Ther 35:63–69PubMedCrossRef

23.

Mullani NA, Herbst RS, O'Neil RG, Gould KL, Barron BJ, Abbruzzese JL (2008) Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: A comparison with 15O-labeled water-measured blood flow. J Nucl Med 49:517–523PubMedCrossRef

24.

Tseng J, Dunnwald LK, Schubert EK et al (2004) 18F-FDG kinetics in locally advanced breast cancer: Correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med 45:1829–1837PubMed

25.

Zasadny KR, Tatsumi M, Wahl RL (2003) FDG metabolism and uptake versus blood flow in women with untreated primary breast cancers. Eur J Nucl Med Mol Imaging 30:274–280PubMedCrossRef

26.

Dunnwald LK, Gralow JR, Ellis GK et al (2008) Tumor metabolism and blood flow changes by positron emission tomography: Relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol 26:4449–4457PubMedCrossRef

27.

Semple SIK, Gilbert FJ, Redpath TW et al (2004) The relationship between vascular and metabolic characteristics of primary breast tumours. Eur Radiol 14:2038–2045PubMedCrossRef

28.

Mankoff DA, Dunnwald LK, Gralow JR et al (2002) Blood flow and metabolism in locally advanced breast cancer: Relationship to response to therapy. J Nucl Med 43:500–509PubMed

29.

Mankoff DA, Dunnwald LK, Gralow JR et al (2003) Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 44:1806–1814PubMed

30.

Jennens RR, Rosenthal MA, Lindeman GJ, Michael M (2004) Complete radiological and metabolic response of metastatic renal cell carcinoma to SU5416 (semaxanib) in a patient with probable von hippel-lindau syndrome. Urologic Oncology: Seminars and Original Investigations 22:193–196PubMedCrossRef

31.

Zhu Z, Li F (2008) Serial PET scans demonstrate the success and limitations of antiangiogenic treatment in a case of lung adenocarcinoma. Clin Nucl Med 33:635–637PubMedCrossRef

32.

Cai W, Chen K, Mohamedali KA et al (2006) PET of vascular endothelial growth factor receptor expression. J Nucl Med 47:2048–2056PubMed

33.

Wang H, Cai W, Chen K et al (2007) A new PET tracer specific for vascular endothelial growth factor receptor 2. Eur J Nucl Med Mol Imaging 34:2001–2010PubMedCrossRef

34.

Nagengast WB, De Vries EG, Hospers GA et al (2007) In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 48:1313–1319PubMedCrossRef

35.

Beer AJ, Haubner R, Goebel M et al (2005) Biodistribution and pharmacokinetics of the αvβ 3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl Med 46:1333–1341PubMed

36.

Beer AJ, Haubner R, Sarbia M et al (2006) Positron emission tomography using [18F]galacto-RGD identifies the level of integrin αvβ3 expression in man. Clin Cancer Res 12:3942–3949PubMedCrossRef

37.

Beer AJ, Lorenzen S, Metz S et al (2008) Comparison of integrin αvβ3 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 49:22–29PubMedCrossRef

38.

Kenny LM, Coombes RC, Oulie I et al (2008) Phase I trial of the positron-emitting arg-gly-asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med 49:879–886PubMedCrossRef

39.

Beer AJ, Grosu A, Carlsen J et al (2007) [18F]galacto-RGD positron emission tomography for imaging of αvβ3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 13:6610–6616PubMedCrossRef

40.

Hood JD, Cheresh DA (2002) Role of integrins in cell invasion and migration. Nat Rev Cancer 2:91–100PubMedCrossRef

41.

Schnell O, Krebs B, Carlsen J et al (2009) Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] galacto-RGD positron emission tomography. Neuro-Oncology 11:861–870PubMedCrossRef

42.

Haubner R, Weber WA, Beer AJ et al (2005) Noninvasive visualization of the activated αvβ3 integrin in cancer patients by positron emission tomography and [18F]galacto-RGD. PLoS Medicine 2:0244–0252CrossRef

43.

Morrison MS, Ricketts S, Barnett J, Cuthbertson A, Tessier J, Wedge SR (2009) Use of a novel arg-gly-asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy. J Nucl Med 50:116–122PubMedCrossRef

44.

Nagengast WB, de Korte MA, Oude Munnink TH et al (2010) 89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine 51:761–767

45.

Meyer CR, Armato SG III, Fenimore CP et al (2009) Quantitative imaging to assess tumor response to therapy: Common themes of measurement, truth data, and error sources. Translational Oncology 2:198–210PubMed

46.

Boellaard R (2009) Standards for PET image acquisition and quantitative data analysis. J Nucl Med 50:11S–20SPubMedCrossRef

47.

Doot RK, Scheuermann JS, Christian PE, et al. (2010) Instrumentation factors affecting variance and bias of quantifying tracer uptake with PET/CT. Medical Physics

48.

Minn H, Zasadny KR, Quint LE, Wahl RL (1995) Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET. Radiology 196:167–173PubMed

49.

Weber WA, Ziegler SI, Thödtmann R, Hanauske A, Schwaiger M (1999) Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med 40:1771–1777PubMed

50.

Crippa F, Gavazzi C, Bozzetti F et al (1997) The influence of blood glucose levels on [18F]fluorodeoxyglucose (FDG) uptake in cancer: a pet study in liver metastases from colorectal carcinomas. Tumori 83:748–752PubMed

51.

Roy F, Beaulieu S, Boucher L, Bourdeau I, Cohade C (2009) Impact of intravenous insulin on 18F-FDG PET in diabetic cancer patients. J Nucl Med 50:178–183PubMedCrossRef

52.

Cobelli C, Foster D, Toffolo G (2001) Tracer kinetic in biomedical research: from data to model. Kluwer Academic/Plenum, Boston

53.

Fahey FH, Kinahan PE, Doot RK, Kocak M, Thurston H, Poussaint TY (2010) Variability in PET quantitation within a multicenter consortium. Med Phys 37:3660–3666PubMedCrossRef

54.

ICRP publication 106 (2008) Radiation dose to patients from radiopharmaceuticals- a third amendment to ICRP publication 53. Ann ICRP Publication 38:1–198

55.

Stabin MG, Sparks RB, Crowe E (2005) OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 46:1023–1027PubMed

56.

Kelloff GJ, Krohn KA, Larson SM et al (2005) The progress and promise of molecular imaging probes in oncologic drug development. Clin Cancer Res 11:7967–7985PubMedCrossRef

57.

Visvikis D, Cheze-LeRest C, Costa D, Bomanji J, Gacinovic S, Ell P (2001) Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET. Eur J Nucl Med 28:1326–1335PubMedCrossRef

58.

Krak NC, Boellaard R, Hoekstra OS, Twisk JWR, Hoekstra CJ, Lammertsma AA (2005) Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging 32:294–301PubMedCrossRef

59.

Lucignani G, Larson SM (2010) Doctor, what does my future hold? the prognostic value of FDG-PET in solid tumours. Eur J Nucl Med Mol Imaging 37:1032–1038PubMedCrossRef

60.

Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: Evolving considerations for PET response criteria in solid tumors. J Nucl Med 50:122S–150SPubMedCrossRef

61.

Schelling M, Avril N, Nährig J et al (2000) Positron emission tomography using [18F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 18:1689–1695PubMed

62.

Seol YM, Kwon BR, Song MK et al (2010) Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemo-radiation therapy. Acta Oncol 49:201–208PubMedCrossRef

63.

Chung MK, Jeong HS, Park SG et al (2009) Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res 15:5861–5868. doi:10.1158/1078-0432.CCR-08-3290 PubMedCrossRef

64.

Hyun SH, Choi JY, Shim YM et al (2010) Prognostic value of metabolic tumor volume measured by 18F- fluorodeoxyglucose positron emission tomography in patients with esophageal carcinoma. Ann Surg Oncol 17:115–122PubMedCrossRef

65.

Larson SM, Erdi Y, Akhurst T et al (1999) Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. the visual response score and the change in total lesion glycolysis. Clinical Positron Imaging (Netherlands) 2:159–171CrossRef

66.

Francis RJ, Byrne MJ, Van Der Schaaf AA et al (2007) Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans. J Nucl Med 48:1449–1458PubMedCrossRef

67.

Cazaentre T, Morschhauser F, Vermandel M et al (2010) Pre-therapy 18F-FDG PET quantitative parameters help in predicting the response to radioimmunotherapy in non-hodgkin lymphoma. Eur J Nucl Med Mol Imaging 37:494–504PubMedCrossRef

68.

Erdi YE, Mawlawi O, Larson SM et al (1997) Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer 80:2505–2509PubMedCrossRef

69.

Daisne J, Sibomana M, Bol A, Doumont T, Lonneux M, Grégoire V (2003) Tri-dimensional automatic segmentation of PET volumes based on measured source-to-background ratios: influence of reconstruction algorithms. Radiother Oncol 69:247–250PubMedCrossRef

70.

Nestle U, Kremp S, Schaefer-Schuler A et al (2005) Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-small cell lung cancer. J Nucl Med 46:1342–1348PubMed

71.

El Naqa I, Yang D, Apte A et al (2007) Concurrent multimodality image segmentation by active contours for radiotherapy treatment planning. Med Phys 34:4738–4749PubMedCrossRef

72.

Hatt M, Cheze le Rest C, Turzo A, Roux C, Visvikis D (2009) A fuzzy bayesian locally adaptive segmentation approach for volume determination in PET. IEEE Trans Med Imaging 28:881–893PubMedCrossRef

73.

Geets X, Lee JA, Bol A, Lonneux M, Grégoire V (2007) A gradient-based method for segmenting FDG-PET images: methodology and validation. Eur J Nucl Med Mol Imaging 34:1427–1438PubMedCrossRef

74.

Montgomery DWG, Amira A, Zaidi H (2007) Fully automated segmentation of oncological PET volumes using a combined multiscale and statistical model. Med Phys 34:722–736PubMedCrossRef

75.

Hatt M, Bailly P, Turzo A, Roux C, Visvikis D (2008) PET functional volume segmentation: a robustness study. IEEE Nuclear Science Symposium Conference Record:4335–4339

76.

Minn H, Clavo AC, Grenman R, Wahl RL (1995) In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck. J Nucl Med 36:252–258PubMed

77.

Nahmias C, Wahl LM (2008) Reproducibility of standardized uptake value measurements determined by 18F-FDG PET in malignant tumors. J Nucl Med 49:1804–1808PubMedCrossRef

78.

Paquet N, Albert A, Foidart J, Hustinx R (2004) Within-patient variability of 18F-FDG: standardized uptake values in normal tissues. J Nucl Med 45:784–788PubMed

79.

Velasquez LM, Boellaard R, Kollia G et al (2009) Repeatability of 18F-FDG PET in a multicenter phase I study of patients with advanced gastrointestinal malignancies. J Nucl Med 50:1646–1654PubMedCrossRef

80.

De Langen AJ, Klabbers B, Lubberink M et al (2009) Reproducibility of quantitative 18F-3′-deoxy-3′- fluorothymidine measurements using positron emission tomography. Eur J Nucl Med Mol Imaging 36:389–395PubMedCrossRef

81.

Kenny L, Coombes RC, Vigushin DM, Al-Nahhas A, Shousha S, Aboagye EO (2007) Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging 34:1339–1347PubMedCrossRef

82.

Hatt M, Cheze-Le Rest C, Aboagye EO et al (2010) Reproducibility of 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET tumor volume measurements. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine 51:1368–1376

83.

Doot R, Allberg K, Kinahan P (2010) Errors in serial PET SUV measurements. J Nucl Med 51:126PCrossRef

84.

Boellaard R, O'Doherty MJ, Weber WA et al (2010) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 37:181–200PubMedCrossRef

85.

Kinahan PE, Doot RK, Wanner-Roybal M et al (2009) PET/CT assessment of response to therapy: tumor change measurement, truth data, and error. Translational Oncology 2:223–230PubMed

86.

Clarke LP, Croft BS, Nordstrom R, Zhang H, Kelloff G, Tatum J (2009) Quantitative imaging for evaluation of response to cancer therapy. Translational Oncology 2:195–197PubMed

87.

Lockhart CM, MacDonald LR, Alessio AM et al (2009) Minimizing instrument calibration error to reduce the effect of variability on PET/CT SUV measurements. J Nucl Med 50:61P

88.

Zimmerman BE, Kinahan PE, Galbraith W, Allberg K, Mawlawi O (2009) Multicenter comparison of dose calibrator accuracy for PET imaging using a standardized source. J Nucl Med 50:123P

89.

Innis RB, Cunningham VJ, Delforge J et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539PubMedCrossRef

90.

Liu C, Pierce Ii LA, Alessio AM, Kinahan PE (2009) The impact of respiratory motion on tumor quantification and delineation in static PET/CT imaging. Phys Med Biol 54:7345–7362PubMedCrossRef

91.

Nehmeh SA, Erdi YE (2008) Respiratory motion in positron emission tomography/computed tomography: a review. Semin Nucl Med 38:167–176PubMedCrossRef

92.

Kinahan PE, Hasegawa BH, Beyer T (2003) X-ray-based attenuation correction for positron emission tomography/computed tomography scanners. Semin Nucl Med 33:166–179PubMedCrossRef

93.

Pan T, Sun X, Luo D (2007) Improvement of the cine-CT based 4D-CT imaging. Med Phys 34:4499–4503PubMedCrossRef

Title: Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials
Authors: Eric O. Aboagye
Fiona J. Gilbert
Ian N. Fleming
Ambros J. Beer
Vincent J. Cunningham
Paul K. Marsden
Dimitris Visvikis
Antony D. Gee
Ashley M. Groves
Laura M. Kenny
Gary J. Cook
Paul E. Kinahan
Melvyn Myers
Larry Clarke
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: European Radiology / Issue 7/2012
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-011-2311-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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