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lesions at a significantly higher rate than conventional their prospective study conducted on 98 NEN patients.
imaging with CT and/or MRI, Ga-DOTA-peptides PET/ 18 F-FDG PET/CT positivity (both in terms of positive/
68
CT is particularly useful in “difficult” situations, such as the negative and quantified by SUVmax) was an independent
identification of the primary tumor in metastatic patients prognostic factor for the prediction of overall survival
after failure of conventional imaging, [4,8,52] the detection of (OS) for NEN patients. With a hazard ratio (HR) of 10
small metastases not always detectable by CT or MRI, [4,52] for risk-of-death for patients with FDG-positive compared
or the characterization of lesions of uncertain nature after with FDG-negative foci, this test exceeded the prognostic
conventional imaging. For these reasons, it is generally value of “conventional” parameters such as Ki-67 labeling
required, for example, to guide the selection of patients index and the presence of liver metastases. Similarly, a
towards those who are potential candidates for radical statistically significant difference in PFS between the
surgery or for liver resection with curative intent. [4,22] In 18 F-FDG-positive and the F-FDG-negative group was
18
the preoperative staging, Ga-DOTATOC PET provides found. Additionally, comparable results were obtained in
68
additional information that significantly influences surgical another study with long-term follow-up, demonstrating an
management in around 20% of patients. [53,54] overall 4 year survival rate of 0% in patients with a positive
18 F-FDG PET scan versus 87% in patients with a negative
On the other hand, F-FDG PET is not routinely used in 18 F-FDG PET scan. These findings have been confirmed
18
[56]
NENs imaging, on the assumption that, due to the low by a prospective study of patients with metastatic NENs
[39]
proliferation rate and low metabolic activity generally seen in which a correlation was noted between F-FDG PET
18
in NETs, F-FDG PET would have a low sensitivity and positivity and worse prognosis in terms of shorter OS and
18
would not provide additional information to conventional PFS. OS was 95% and 95% at 1 and 2 years, respectively,
CT and SSTR-based imaging. [11,38] Indeed, F-FDG-based for patients with a negative F-FDG PET scan, versus
18
18
functional imaging demonstrates a low overall diagnostic 72% and 42% at 1 and 2 years, respectively, for patients
sensitivity for NENs (58% for F-FDG PET, 66% with a positive F-FDG PET scan. PFS was 87% and 75%
18
18
[39]
for F-FDG PET/CT), and in general, SSTR-based at 1 and 2 years, respectively, for patients with a negative
[38]
18
functional imaging with Ga-DOTA-peptides has superior 18 F-FDG PET scan, versus 7% and 0% at 1 and 2 years,
68
accuracy in NENs diagnosis and staging compared with respectively, for patients with a positive F-FDG PET
18
18 F-FDG PET/CT. Nonetheless, it is known that one of scan. [2]
the main limitations of SSTR-based PET/CT with Ga-
68
DOTA-peptides lies in the detection of poorly differentiated 18 F-FDG PET may be useful even in a non-metastatic
NECs, which frequently show a low expression of SSTRs setting, to predict the prognosis in surgical patients. In
on cell membrane. Such limitation can be overcome by a study conducted on patients with pancreatic NENs
combining the use of F-FDG with Ga-DOTA-peptides. 18 F-FDG PET SUVmax correlated with tumor grade and
18
68
The combination of 68 Ga-DOTATATE PET/CT and also appeared to be significantly related to postoperative
18 F-FDG PET/CT improves the diagnostic accuracy over disease-free survival (P = 0.0463). [34]
single tracer-PET/CT. Indeed, Kayani et al. reported a
[38]
sensitivity of 82% for Ga-DOTATATE PET/CT alone Predictive relevance
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and of 66% for F-FDG PET/CT alone compared with Predicting the course of a metastatic NEN is difficult.
18
92% for double tracer ( Ga-DOTATATE plus F-FDG) Aggressive treatment should be proposed to all patients
68
18
PET/CT. in good overall health with high-grade NECs because of
their rapidly progressive behavior. Different therapeutic
Prognostic relevance strategies may instead be proposed to patients with well-
Combining F-FDG PET/CT with Ga-DOTA-peptides differentiated NETs, which may show a variable range of
68
18
PET/CT can provide additional prognostic information. malignant behavior. Due to the fact that available treatments
may have significant long-term toxicity, it is important to
A high SSTR expression does not represent per se a distinguish between rapidly progressive NENs, for which
prognostic parameter in terms of PFS. F-FDG uptake, active treatment is necessary and relatively indolent NENs,
[55] 18
conversely, seems to be related to higher Ki-67 index, which may be treated more conservatively.
higher proliferation rate and worse prognosis. [12,14]
68 Ga-DOTA-peptide PET/CT, depicting the amount of
In a first study by Pasquali et al., a positive F-FDG SSTR expression on NEN cells, has been proposed as a
18
[12]
PET scan was associated with early progression and a predictive tool for both SSAs treatment and PRRT. [22,57]
shorter survival. Ninty-three percent of patients with a While SSTR-based functional imaging positivity is not
positive F-FDG PET scan had a progressive disease required before the start of SSAs therapy, it is a basic
18
within 6 months vs. 8,7% of patients with a negative requirement for PRRT with beta-emitting radiolabeled
18 F-FDG PET scan. Similarly, 95% of patients with a SSAs. [3,8,22,58] Due to its pharmacokinetics, PRRT is
positive F-FDG PET scan were alive at 2 years vs. 42% effective only in SSTR-expressing lesions. SUVmax
18
[59]
of patients with a negative F-FDG PET scan. These measured on PET imaging with Ga-DOTA-peptides
68
18
observations were confirmed by Binderup et al. in exactly correlates with the number of SSTR on tumor
[39]
324
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦