Multiparametric evaluation of tumour hypoxia and perfusion using[15O]H2O and [18F]FAZA PET in NSCLC patients

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Abstract

Objectives [18F]fluoroazomycin-arabinoside ([18F]FAZA) is a PET tracer, proposed for quantifying tumour hypoxia. However, as hypoxia is associated with decreased perfusion, delivery of [18F]FAZA might be compromised, potentially disturbing the association between tissue hypoxia and [18F]FAZA uptake. This study aimed to gain insight in the relationship between tumour perfusion and [18F]FAZA uptake. Methods Eight patients with non-small cell lung cancer (NSCLC) underwent dynamic [15O]H2O and [18F]FAZA scans with arterial sampling. Parametric analyses were performed to generate quantitative 3D images of both perfusion and volume of distribution (VT) of [18F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high VT using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results 11 malignant lesions were identified in 8 patients. Average perfusion and VT across all lesions were 0.46±0.20 mL/mL/min and 0.95±0.31, respectively. The average of all median values across all lesions were 0.38±0.15 mL/mL/min and 0.87±0.18 for perfusion and VT, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where VT of [18F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and VT were either both decreased or increased. Conclusions Spatial variation of [18F]FAZA uptake is not necessarily inversely related with perfusion. Decreased perfusion might thus result in perfusion limited delivery of [18F]FAZA. In conclusion, multiparametric evaluation of the spatial distribution of both perfusion and [18F]FAZA uptake may be essential for understanding the [18F]FAZA signal.
Original languageEnglish
JournalJournal of Nuclear Medicine
Volume56
Publication statusPublished - 2015

Cite this

@article{1775d010dec64e51abaf6986d9cedb3f,
title = "Multiparametric evaluation of tumour hypoxia and perfusion using[15O]H2O and [18F]FAZA PET in NSCLC patients",
abstract = "Objectives [18F]fluoroazomycin-arabinoside ([18F]FAZA) is a PET tracer, proposed for quantifying tumour hypoxia. However, as hypoxia is associated with decreased perfusion, delivery of [18F]FAZA might be compromised, potentially disturbing the association between tissue hypoxia and [18F]FAZA uptake. This study aimed to gain insight in the relationship between tumour perfusion and [18F]FAZA uptake. Methods Eight patients with non-small cell lung cancer (NSCLC) underwent dynamic [15O]H2O and [18F]FAZA scans with arterial sampling. Parametric analyses were performed to generate quantitative 3D images of both perfusion and volume of distribution (VT) of [18F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high VT using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results 11 malignant lesions were identified in 8 patients. Average perfusion and VT across all lesions were 0.46±0.20 mL/mL/min and 0.95±0.31, respectively. The average of all median values across all lesions were 0.38±0.15 mL/mL/min and 0.87±0.18 for perfusion and VT, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where VT of [18F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and VT were either both decreased or increased. Conclusions Spatial variation of [18F]FAZA uptake is not necessarily inversely related with perfusion. Decreased perfusion might thus result in perfusion limited delivery of [18F]FAZA. In conclusion, multiparametric evaluation of the spatial distribution of both perfusion and [18F]FAZA uptake may be essential for understanding the [18F]FAZA signal.",
keywords = "arabinoside, classification, fluorine 18, human, hypoxemia, hypoxia, intralesional drug administration, molecular imaging, neoplasm, non small cell lung cancer, nuclear medicine, oxygen 15, patient, perfusion, sampling, society, tracer, volume of distribution",
author = "R Iqbal and G Kramer and E Verwer and M Huisman and {De Langen}, J and I Bahce and A Windhorst and A Lammertsma and O Hoekstra and R Boellaard",
year = "2015",
language = "English",
volume = "56",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",

}

TY - JOUR

T1 - Multiparametric evaluation of tumour hypoxia and perfusion using[15O]H2O and [18F]FAZA PET in NSCLC patients

AU - Iqbal, R

AU - Kramer, G

AU - Verwer, E

AU - Huisman, M

AU - De Langen, J

AU - Bahce, I

AU - Windhorst, A

AU - Lammertsma, A

AU - Hoekstra, O

AU - Boellaard, R

PY - 2015

Y1 - 2015

N2 - Objectives [18F]fluoroazomycin-arabinoside ([18F]FAZA) is a PET tracer, proposed for quantifying tumour hypoxia. However, as hypoxia is associated with decreased perfusion, delivery of [18F]FAZA might be compromised, potentially disturbing the association between tissue hypoxia and [18F]FAZA uptake. This study aimed to gain insight in the relationship between tumour perfusion and [18F]FAZA uptake. Methods Eight patients with non-small cell lung cancer (NSCLC) underwent dynamic [15O]H2O and [18F]FAZA scans with arterial sampling. Parametric analyses were performed to generate quantitative 3D images of both perfusion and volume of distribution (VT) of [18F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high VT using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results 11 malignant lesions were identified in 8 patients. Average perfusion and VT across all lesions were 0.46±0.20 mL/mL/min and 0.95±0.31, respectively. The average of all median values across all lesions were 0.38±0.15 mL/mL/min and 0.87±0.18 for perfusion and VT, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where VT of [18F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and VT were either both decreased or increased. Conclusions Spatial variation of [18F]FAZA uptake is not necessarily inversely related with perfusion. Decreased perfusion might thus result in perfusion limited delivery of [18F]FAZA. In conclusion, multiparametric evaluation of the spatial distribution of both perfusion and [18F]FAZA uptake may be essential for understanding the [18F]FAZA signal.

AB - Objectives [18F]fluoroazomycin-arabinoside ([18F]FAZA) is a PET tracer, proposed for quantifying tumour hypoxia. However, as hypoxia is associated with decreased perfusion, delivery of [18F]FAZA might be compromised, potentially disturbing the association between tissue hypoxia and [18F]FAZA uptake. This study aimed to gain insight in the relationship between tumour perfusion and [18F]FAZA uptake. Methods Eight patients with non-small cell lung cancer (NSCLC) underwent dynamic [15O]H2O and [18F]FAZA scans with arterial sampling. Parametric analyses were performed to generate quantitative 3D images of both perfusion and volume of distribution (VT) of [18F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high VT using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results 11 malignant lesions were identified in 8 patients. Average perfusion and VT across all lesions were 0.46±0.20 mL/mL/min and 0.95±0.31, respectively. The average of all median values across all lesions were 0.38±0.15 mL/mL/min and 0.87±0.18 for perfusion and VT, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where VT of [18F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and VT were either both decreased or increased. Conclusions Spatial variation of [18F]FAZA uptake is not necessarily inversely related with perfusion. Decreased perfusion might thus result in perfusion limited delivery of [18F]FAZA. In conclusion, multiparametric evaluation of the spatial distribution of both perfusion and [18F]FAZA uptake may be essential for understanding the [18F]FAZA signal.

KW - arabinoside

KW - classification

KW - fluorine 18

KW - human

KW - hypoxemia

KW - hypoxia

KW - intralesional drug administration

KW - molecular imaging

KW - neoplasm

KW - non small cell lung cancer

KW - nuclear medicine

KW - oxygen 15

KW - patient

KW - perfusion

KW - sampling

KW - society

KW - tracer

KW - volume of distribution

M3 - Article

VL - 56

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

ER -