Page 46 - Read Online

proteins. Once internalized, F-FDG is phosphorylated to be considered in imaging interpretation. Moreover, as
[8]
18
18 F-FDG-6-phosphate which cannot be further metabolized SSTRs are also expressed in peritumoral vessels and in
and remains trapped in the cell. [16] inflammatory and immune cells, false-positive findings
may be constituted by non-NETs and inflammatory
High rates of glycolysis are found in many malignant diseases. That being stated, the reported sensitivity and
[8]
tumor cells. Compared with normal cells, malignant specificity of PET/CT with Ga-DOTA-peptides in the
[17]
68
cells have an increased number of cell surface glucose diagnosis of NETs are 96% and 100%, respectively.
[24]
transporter proteins and increased intracellular Such outcomes are superior to that obtained with
glycolytic enzyme levels, including hexokinase and somatostatin receptor scintigraphy (SRS) and CT in NENs
phosphofructokinase. [15,16] In clinical practice, therefore, diagnosis, staging, and restaging. The synthesis of Ga-
68
[25]
18 F-FDG is often used to distinguish malignant from DOTA-peptides is relatively easy and does not require
normal tissues, to stage many types of neoplasms, and to an on-site cyclotron. Ga (physical half-life 68.3 min) is
68
detect recurrence after treatment. Moreover, F-FDG eluted from an in-house Ga generator (physical half-life
[18]
18
68
uptake, reflecting glucose metabolism, has been associated 270.8 days by electron capture) that allows a continuous
with higher cellular proliferative activity, increased tumor tracer production. Ga-DOTA-peptides are administered
[8] 68
aggressiveness, and a less favorable prognosis. However, via intravenous injection and images are acquired between
it should be noted that the uptake of F-FDG varies greatly 45 and 90 min after injection. The activity administered
18
[8]
for different tumor types and increased F-FDG uptake is in adults is 1.5-3 MBq per kg (100-200 MBq). To avoid
18
[8]
not necessarily specific for neoplasms. Increased F-FDG possible SSTR blockade, patients undergoing PET/CT
18
uptake may also be due to inflammatory processes, with Ga-DOTA-peptides should stop SSAs treatment,
68
muscle contraction and brown fat activation. [8,15] From with an interval time depending on the type of drug used
the technical point of view, F-FDG is administered (1 day for short-acting SSAs and 3-4 weeks for long-acting
18
via intravenous injection (standard doses: 10-20 mCi of SSAs). No fasting before the injection of radiolabeled
[8]
[19]
18 F-FDG, 0.14-0.21 mCi/kg of body weight) and images SSAs is needed. [8]
are acquired approximately 60 min after injection to allow
18 F-FDG clearance from the blood pool and sufficient FOCUS ON F-FDG AND GA PET/CT IN
68
18
18
18 F-FDG uptake in the target tissues ( F-FDG half-life is NENs
109 min). In order to minimize competitive inhibition
[15]
of F-FDG uptake by glucose, patients should be fasted At present, F-FDG PET/CT is not routinely recommended
18
18
for at least 6 h prior to F-FDG injection. Blood glucose for NENs imaging. The generally slow-growing behavior
18
levels are routinely assessed before starting the imaging, of this tumor type led to the hypothesis of a lower glycolytic
and 200 mg/dL is considered the maximum cutoff point. activity compared with many other malignancies, and
[16]
Adequate pre-hydration is important to reduce F-FDG accordingly, of a lower sensitivity for F-FDG PET in this
18
18
concentration in urine and to reduce radiation dose to the setting. This notwithstanding, F-FDG PET/CT shows a
18
patient. [16] positive result in about 60% of NEN patients.
68
68 Ga-DOTA-peptides 18 F-FDG and Ga PET/CT and primary tumor
68 Ga-DOTA-peptides are radiolabeled SSAs capable of site
specifically binding to SSTR, which are overexpressed NENs which arise in the thoracic region have a higher
on the surface of NET cells, thus permitting functional proportion of high-grade versus low-grade NENs (18-
[16]
imaging and therapeutic targeting of NETs. Five different 23.0% vs. 1-2.0% of all lung neoplasms), as has been
[20]
SSTR subtypes have been identified (SSTR1 to SSTR5), reported in a review by Fisseler-Eckhoff and Demes. In
[26]
but SSTR2 is the predominant receptor subtype in NETs. this context it should be observed that poorly differentiated
[21]
Many Ga-DOTA-peptides have been developed for PET NENs are usually F-FDG-avid and demonstrate less
18
68
imaging of NETs. The most widely employed in the 68 Ga-DOTA-peptide uptake. Among indolent, low-grade
[8]
clinical setting are Ga-DOTANOC ([DOTA0,1-Nal3]- thoracic NETs, i.e. typical bronchial carcinoids, a low
68
octreotide), 68 Ga-DOTATATE ([DOTA0,Tyr3,Thr8]- glucose turnover is common. In these histotypes, Ga-
68
[27]
octreotide), and 68 Ga-DOTATOC ([DOTA0,Tyr3]- DOTA-peptide PET/CT demonstrates a superior diagnostic
octreotide). The major difference among these power over F-FDG PET/CT, being able to correctly
[8]
18
compounds relies on a slightly different affinity to SSTR discriminate endobronchial neoplasms from adjacent
subtypes. Although all Ga-DOTA-peptides can bind to atelectasis. The good correlation of F-FDG and Ga-
68
68
18
SSTR2, Ga-DOTATOC and Ga DOTANOC also bind DOTATATE uptake with tumor grade in pulmonary NETs
68
68
to SSTR5, and Ga-DOTANOC has additional affinity for justifies their clinical use as an aid in the identification,
68
SSTR3. Physiological Ga-DOTA-peptides uptake is both at initial staging and during follow-up and evaluation
[22]
68
evident in liver, spleen, pituitary, thyroid, kidneys, adrenal of treatment results, of the presence of aggressive tumors
glands, salivary glands, stomach wall, intestine, and or dedifferentiated areas within a low grade neoplasm. [28]
pancreas. In particular, a physiological focal location of
[23]
uptake is in the pancreatic uncinate process, which must NENs which arise in the gastro-entero-pancreatic (GEP)
322
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦