Chemistry Reference
In-Depth Information
124
I
O
2
N
N
124
I
I
OH
N
O
SiO
2
nanoparticle
HO
O
OH
OH
I
H
2
N
O
O
NH
2
OH
HN
[
124
I]-T3
[
124
I]-IAZGP
O
NH
O
N
NH
2
O
O
N
124
I
O
N
124
I
NH
O
N
H
N
N
O
HO
NH
HN
F
O
124
I
O
O
O
NH HN
HO
O
HN
OH
O
CO
2
H
[
124
I]-PUH71
[
124
I]-FIAU
[
124
I]-cRGDY-PEG-dots
fIgure 5.16
A selection of
124
I-based radiopharmaceuticals currently in clinical trials.
showed promising high specificity and selectivity [53, 181]. The non-hodgkin's lymphoma drug Puh71 was radioiodinated
with
124
I and used as a tool in clinical trials to evaluate the biodistribution of the drug in different compartments of the body
and to measure blood clearance times [53].
2′-Fluoro-2′-deoxy-1β-d-arabinofuranosyl-5-iodouracil was labelled with
124
I (
124
I-FIAu) to evaluate its biodistribution
and localisation in infectious tissue. It has also been used to image herpes simplex virus type 1 thymidine kinase (hsV1-tk)
gene expression [53, 182, 183]. A more unique entry into recent clinical trials is
124
I-
c
RGdY-PEG-dots, which are silica
nanoparticles that are conjugated through polyethyleneglycol (PEG) spacer groups to
124
I labelled
cyclic
-arginine-glycine-
aspartic acid-tyrosine (
c
RGdY) peptides for targeting melanoma [53, 184]. Also in clinical trials is
124
I labelled humanised
A33 (
124
I-huA33) antibody for radioimmunodetection of colorectal cancer [53, 185].
124
I-iodo-azomycin-galactopyranoside
(
124
I-IAZGP) is being evaluated in clinical trials for hypoxic tumour imaging in a variety of cancers [53, 186], and the similar
compound 1-α-d-(5-deoxy-5-[
124
I]iodo-arabinofuranosyl)-2-nitroimidazole (
124
I-IAZA, not in clinical trials) is also being
investigated for tumour hypoxia imaging [187]. The
124
I-labelled antibody 8h9 is being investigated for peritoneal cancer, and
124
I-labelled monoclonal antibody Mu11-1 F4 for Al amyloidosis (primary light-chain amyloidosis) [53]. Finally,
124
I-labelled
tri-iodothyronine (T3) is a thyroid hormone that is currently being used to study T3 metabolism [53]. These examples illus-
trate the large differences between radiometals and radioiodine in their methods of incorporation as radiopharmaceuticals.
5.8.2
recent
124
Iodine work
As previously discussed, matched isotope pairs for imaging/dosimetry and therapy are an integral part of nuclear medicine.
Finding an isotope pair with identical chemistry is crucial in order to retain identical biological activity, as seen with the
86
Y/
90
Y isotope pair. In a similar scenario,
124
I/
131
I can be used as a matched isotope pair as both isotopes are chemically iden-
tical and can be radioiodinated in an identical fashion, as demonstrated with MIBG and various antibodies [188].
124
I has also
recently been shown to be a very effective matched isotope pair for
131
I metastatic differentiated thyroid cancer (dTC)
treatment, in order to obtain accurate dosimetry data and minimise patient absorbed dose [189]. Currently, one of the most
active areas of
124
I research is in antibody labelling, as observed in the current clinical trial offerings [53]. Various antibodies
are being investigated such as the anti-Cd20 monoclonal antibody rituximab (Mabthera
®
) for imaging B-cell populations in
rheumatoid arthritis [190] and the anti-hER2 C6.5 diabody for obtaining predictive dosimetry data for radioimmunotherapy
with antibody conjugates such as herceptin [191]. In a very interesting recent study, the
124
I-labelled antibody cG250 (for
renal cancer) was used to compare
in vivo
PET imaging dosimetry with
in vitro
autoradiography and γ-counting methods,
and it was demonstrated that both methods yielded very similar results and that PET/CT can be reliably used for obtaining
quantitative dosimetry data [192]. As with
86
Y, one of the major strengths of
124
I lies with its application in PET dosimetry
studies with a matched isotope pair. A more novel application is the use of
124
I-labelled chitosan, which is a polysaccharide
used as an ocular delivery agent [193]. studies comparing
124
I-chitosan with
124
I-naI showed a twofold increase in ocular
retention of the labelled chitosan when compared to free radioiodide [193].
