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Topic: Neuroendocrine Tumors

Double tracer PET/CT: what is it and what does it mean?

Mattia Pellicciari, Silvia Ortolani, Elisabetta Grego, Giampaolo Tortora, Sara Cingarlini
Department of Clinical Oncology, Comprehensive Cancer Network, G. B. Rossi University Hospital, University of Verona, 37134 Verona, Italy.
Corresponding Author: Dr. Sara Cingarlini, Department of Clinical Oncology, Comprehensive Cancer Network, G. B. Rossi University Hospital,
University of Verona, Piazzale L. A. Scuro 10, 37134 Verona, Italy. E-mail: sara.cingarlini@ospedaleuniverona.it

A B S T R AC T
68 Ga-DOTA-peptide PET/CT is a recommended imaging modality in the workup of neuroendocrine neoplasms (NENs), which
shows high diagnostic sensitivity and is a strong predictor of successful somatostatin receptor directed treatments. Although not
routinely recommended, reliable evidences show that F-FDG PET/CT can provide complementary information in this setting
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with the ability to discriminate slow-proliferating tumors from aggressive, rapidly-proliferating tumors. Further, it has been
proposed as an independent prognostic factor for the prediction of either overall survival or progression free survival. In this
review, we provide insight into the biologic significance of Ga-DOTA-peptides and F-FDG uptake, and of the use of double
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tracer ( Ga-DOTA-peptides plus F-FDG) PET/CT in the clinical evaluation of patients affected by NENs.
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Key words: Ga-DOTATOC PET/CT; F-FDG PET/CT; neuroendocrine neoplasms
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INTRODUCTION NENs. Tracers which exploit SSTR expression
[10]
( Ga-DOTA-peptide) therefore have been employed
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Neuroendocrine neoplasms (NENs) represent a group of in the diagnosis and staging of well-differentiated
heterogeneous and infrequent tumors, with an estimated neuroendocrine tumors (NETs). Poorly-differentiated
incidence of 5.86 per 100,000 per year, that most neuroendocrine carcinomas (NECs), which exhibit a
[1]
frequently originate from neuroendocrine cells of the higher proliferative activity and a loss of neuroendocrine
upper airways, the small intestine, the duodenum and the features including the expression of SSTRs, are more
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pancreas. NENs are generally asymptomatic in the early, suited to the use of F-Fluoro-2-deoxyglucose ( F-FDG)
[2]
[8]
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localized stages (with the exception of a small minority of imaging. In fact, reported F-FDG sensitivity is low in
[11]
NENs, represented by so-called functioning NENs, which well-differentiated NETs, and significantly improved
[12]
actively secrete bioactive substances and can present in poorly-differentiated NECs. Therefore, it has been
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with related signs and symptoms, such as flushes and hypothesized that F-FDG-based molecular imaging may
diarrhea). Functioning NENs are often discovered after differentiate between more biologically aggressive NENs,
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the development of symptomatic metastases elsewhere which exhibit greater F-FDG uptake, and more slowly-
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in the body, [2,3] which occur most frequently in the lymph growing NENs, which exhibit less intense F-FDG uptake.
nodes, liver, and bones. [4,5] NENs may exhibit a variety of However, retrospective reports evaluating the prognostic
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[13,14]
biological behaviors in that they may be aggressive and value of F-FDG have provided discordant results.
rapidly growing or indolent and a long survival time (on 18 F-FDG AND GA: BIOLOGICAL AND
[6]
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the order of years) is not uncommon in patients with slowly TECHNICAL ASPECTS
progressing tumors. The majority of NENs express
[7]
somatostatin receptors (SSTR) on the cell membrane, 18 F-fluoro-2-deoxyglucose ( F-FDG)
[8]
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which makes them ideal targets for both functional 18 F-FDG is the most commonly used radiopharmaceutical
imaging and therapeutic applications with radiolabeled tracer for PET imaging in clinical oncology. It is a
[15]
somatostatin analogues (SSAs). [4,9] The level of SSTR glucose analogue labeled with positron-emitting 18F. The
expression appears to depend on tumor differentiation, compound is taken up into cells by glucose transporter
with increased numbers of receptors expressed in well-
differentiated NENs compared to poorly-differentiated This is an open access article distributed under the terms of the Creative
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How to cite this article: Pellicciari M, Ortolani S, Grego E, Tortora G,
Cingarlini S. Double tracer PET/CT: what is it and what does it mean?
DOI: J Cancer Metasta Treat 2016;2:321-8.
10.20517/2394-4722.2016.45
Received: 17-07-2016; Accepted: 15-08-2016
©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 321