Tumour hypoxia imaging with
18
F-fluoroazomycinarabino-
furanoside PET/CT in patients with locally advanced
rectal cancer
Birgitte M. Havelund
a,d
, Paw C. Holdgaard
b
, Søren R. Rafaelsen
c
,
Lise S. Mortensen
e
, Jørn Theil
f
, Dirk Bender
f
, John Pløen
a
,
Karen-Lise G. Spindler
a,d
and Anders Jakobsen
a,d
Objective The aim of this study was to investigate
the feasibility of
18
F-fluoroazomycinarabinofuranoside
(
18
F-FAZA) positron emission tomography (PET)/
computed tomography (CT) in patients with locally
advanced rectal cancer.
Materials and methods The study included 14 patients
with locally advanced rectal cancer. Before
chemoradiotherapy, PET/CT with
18
F-FAZA was performed
with static 15 min images 2 h after injection of
18
F-FAZA. Attenuation correction was obtained
with a low-dose CT, and a contrast-enhanced CT was
performed immediately after the PET scan.
Results
18
F-FAZA uptake [mean and maximum
standardized uptake value (SUV
mean
) and (SUV
max
)] was
significantly higher in rectal tumours than in both muscles
(P < 0.003) and normal intestinal walls (P <5 ¾ 10
–5
).
The tumour to muscle (T/M) ratios ranged from 1.19 to
3.05 with a mean of 1.97, whereas the tumour to intestinal
wall (T/I) ratios had values of 1.73–5.81 with a mean of 2.83.
Intense activity accumulating in the bladder produced
obvious scattered activity, which spread into the surrounding
tissue. Tumour volumes excluding scatter were therefore
determined, in which the SUV
max
and SUV
mean
were also
significantly higher than in both muscles (P< 0.004) and
normal intestinal walls (P <2 ¾ 10
–5
) and had T/M ratios
of 1.19–2.72 with a mean of 1.85 and T/I ratios of 1.71–5.40
with a mean of 2.67. The individual SUV
max
, SUV
mean
, T/M
and T/I values were significantly higher in the entire tumour
volume compared with the tumour volume adjusted for
scatter from the urinary bladder (P < 0.005), although the
absolute differences were small.
Conclusion
18
F-FAZA PET/CT is feasible for visualization
of hypoxia in patients with rectal cancer, but scattered
activity from the urinary bladder should be taken into
consideration. Nucl Med Commun 34:155–161 c 2013
Wolters Kluwer Health | Lippincott Williams & Wilkins.
Nuclear Medicine Communications 2013, 34:155–161
Keywords:
18
F-fluoroazomycinarabinofuranoside, hypoxia, imaging, PET,
radiotherapy, rectal neoplasm
Departments of
a
Oncology,
b
Nuclear Medicine,
c
Radiology, Vejle Hospital,
Vejle,
d
Institute of Regional Health Services Research, University of Southern
Denmark, Odense, Departments of
e
Experimental Clinical Oncology and
f
Department of Nuclear Medicine and PET Centre, Aarhus University Hospital,
Aarhus C, Denmark
Correspondence to Birgitte Mayland Havelund, Department of Oncology,
Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark
Tel: +45 794 06038; fax: +45 794 06907;
e-mail: birgitte.mayland.havelund@slb.regionsyddanmark.dk
Received 12 July 2012 Revised 27 August 2012 Accepted 24 October 2012
Introduction
The standard treatment of locally advanced rectal cancer
is long-course chemoradiotherapy (CRT) followed by
surgery based on total mesorectal excision. Preoperative
CRT reduces the risk of local recurrence, but the
individual response to CRT varies [1]. A minor group of
patients will experience complete tumour response
verified by pathological examination of the surgical
specimens and may therefore be candidates for watchful
waiting without surgery [2,3]. A better method for
selecting these patients is thus of prime importance.
Tumour hypoxia is an acknowledged phenomenon in the
development of malignant tumours [4], and hypoxia-
associated radiotherapy (RT) resistance has been known
for decades [5]. The clinical importance of hypoxia in
relation to RT is best established in squamous cell
carcinoma of the head and neck, in which tumour hypoxia
is linked to poor survival after RT [6]. Tumour hypoxia
has been identified in adenocarcinomas of the rec-
tum [7,8], but the role of hypoxia in relation to CRT
for rectal cancer remains to be determined.
Previously, direct measurement of the oxygen tension in
the tumour using a polarographic ‘Eppendorf ’ needle
electrode was considered the gold standard method for
measuring hypoxia [9]. Another commonly used method
is injection of nitromidazole derivates (e.g. pimonidazole)
and subsequent immunohistochemical visualization in
the resected tumour or in biopsies [9].
Noninvasive measurement of hypoxia by PET scans using
hypoxia-specific tracers is attractive because of the
Data were presented at the ESMO 14th World Congress on Gastrointestinal
Cancer (June 27–30, 2012), and have been published as an abstract in Ann
Oncol 2012; 23(Suppl 4) (
18
F-FAZA in rectal cancer, abstract no. P-0298).
Original article
0143-3636 c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MNM.0b013e32835bd5bc
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.