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Mehdi akhlaghi,PET radiotracers other than FDG
1. PET radiopharmaceuticals beyond
FDG, Why they are important?
How they are prepared?
By: Mehdi Akhlaghi
Organic & Radio chemist, PhD
Tehran University of Medical Sciences
November 12-14, 2014
2. At present, more than 95% of PET studies worldwide are performed in
oncologic patients, using F-18 Fluorodeoxyglucose (FDG). But, despite its
high diagnostic accuracy in determining the pivotal role in the restaging
(and staging), FDG is handicapped by false negative and positive results,
creating limitations in the differential diagnosis of cancer.
Moreover, PET- FDG shares finding with all the other diagnostic techniques
(CT, MRI) to answer all the questions of the oncologist, the surgeon, and the
radiotherapist. It cannot function alone, either in the diagnostic field, or in
giving all the information connected with prognosis and pursue a “tailored
strategy” for each patient. Therefore, despite its primary role, there is a
wide range of indications in oncologic patients that other radiotracers may
be useful, and in this lecture we shall try to understand them.
In oncology, the results concerning neoplastic lesions not detected by the
procedure are called false negative results of FDG. Conversely, false
positive results are those connected with benign lesions, showing FDG
uptake.
Introduction
3. Introduction
A hybrid PET-CT scanner permits higher accuracy with respect
to PET alone, because of the added morphostructural
information and the anatomical location of the FDG activity
allowed by CT.
Despite using PET-CT, false negative and false positive results
are, however, present. An improvement in sensitivity and
specificity with the use of PET radiotracers other than FDG, can
therefore significantly increase overall diagnostic accuracy.
4. Introduction
With respect to methodology, many causes can affect
glucose kinetics, creating difficulties in FDG utilization.
The major problem is; high glucose serum levels, as
observed, in particular, in diabetes.
other conditions can determine an unfavorable
distribution of FDG. For example a nonspecific FDG
uptake requires correct timing for a reliable evaluation
of patients who have undergone surgery, adiotherapy,
or chemotherapy or have inflammation.
Therefore, the availability of radiotracers not affected
by conditions such as high glucose levels,
inflammation, altered permeability or vascularity, can
help in finding a rationale to choose an alternative to
FDG. Thus, a more effective clinical value can be
reached, for example, in diabetic patients, or when the
clinical history of the patient suggests that the analysis
obtained by using FDG is not reliable.
5. Introduction
False negative results of PET-FDG are mainly due to lesions that are too
small to be PET’s spatial resolution, which is usually above 5 mm. It has
to be pointed out that the positive indicators as FDG, i.e., radiotracers
with a higher uptake in lesions than in the surrounding normal tissue,
can also occasionally detect lesions that are less than the spatial
resolution value.
the detectability of the lesion depends mainly on the
Lesion/background (L/B) ratio. It depends more on the uptake
mechanism of the radiotracer than on the PET scanner. With respect to
FDG, a higher L/B can be achieved by different radiotracers allowing a
higher tumor uptake and/or a lower background activity.
Radiotracers Allowing a Higher Tumors Uptake
Radiotracers Allowing a Lower Background
Radiotracers Allowing a Increased Specificity
Radiotracers Allowing an Improved Diagnostic Accuracy
The choice of an alternative radiotracer should be based on a deep and
strong knowledge of the pathophysiological premises of their uptake
mechanism.
31. Ga-68-labeling of peptides
• Y-90-labeling of peptides
• Lu-177- labeling of peptides
• Cu-64-radionuclide purification
• Cu-64-radiolabeling
• C-11-methylation
• C-11-methyliodide production
• F-18-labeling
• I-123/124/131-labeling
• automated generator elutions
Production of any 11C tracer, e.g.
[11C]Methionine, [11C]Choline, [11C]DASP or
[11C]Raclopride and any 18F tracer by
nucleophilic or electrophilic substitution,
e.g. [18F]Dopa, [18F]FDG, [18F]FLT, [18F]Miso, et
34. •[18F]NaF
•[18F]FLT
•[18F]FMiso
•[18F]FCholine
•[18F]FA(FAcetate)
•[18F]FET
•[18F]FES
•[18F]SFB
•[18F]MPPF (HPLC)
•[18F]Fallypride (HPLC)
•[18F]FHBG
•[18F]-L-DOPA
The Synthera employs a single use
disposable system, the IFP™ (integrated
fluidic processor) and a set of commercially
available reagents for the synthesis of a
wide variety of compounds: FDG, NaF, FLT,
FCH, FDOPA, FMISO and others
35. [18F]FDG
2–[18F]fluorodeoxyglucose
Use: Measure of glycolysis
Yield*: n=6 RCY=61.0% +/– 12.9%
[18F]FAC
2–deoxy–2–[18F]fluoro–β–D–arabinofuranosyl
Use: Assay for deoxycytidine kinase
Yield*: n=5 RCY=31.3% +/– 6.0%
[18F]FMAU
2–deoxy–2–[18F]flouro–5–methyl–1–β–L arabinofuranosyl uracil
Use: Monitor cellular proliferation; PET reporter probe for reporter gene imaging
Yield*: n=3 RCY=45.2% +/– 1.5%
[18F]FEAU
[18F]SFB
N–succinimidyl–4–[18F]fluorobenzoate
Use: Most actively used prosthetic group for protein/peptide/antibody labeling
Yield*: n=5 RCY=69.5% +/– 9.1%
[18F]FLT
[18F]fluorothymidine
Use: Monitor cellular proliferation
Yield*: n=5 RCY=11.9% +/– 1.6%
[18F]FHBG
[18F]Fallypride
*All data reported is un-optimized. Radiochemical yield (RCY) is decay corrected.
100% starting activity defined by [18F]fluoride released into reactor vial 1,
after[18F]fluoride trap and release.
SOFIE–optimized protocols are available with every ELIXYS purchase.
Check back for a list of reagent kits coming soon!