Chemistry Reference
In-Depth Information
common method for evaluating the stability of radioiodinated compounds is to incubate them with blood serum and monitor
the decomposition over time with radio-hPlC and radio-TlC methods (similar to evaluation of radiometal complex sta-
bility) [207]. Biochemical dehalogenation
in vivo
is common and occurs to varying degrees depending on the stability of the
C-I bond [208]. When substituting an aromatic hydrogen for radioiodine, the resulting C-I bond is weaker than the C-h it
replaces; therefore, it is more prone to decomposition and dehalogenation, with aromatic and vinyl iodinations being most
stable (phenyl-h = ~460 kJ/mol, phenyl-I = 268 kJ/mol, alkyl-I = 222 kJ/mol, vinyl-I = 297 kJ/mol) [208, 209].
5.8.5
124
Iodine summary
124
I-radioiodination of various small molecule agents, prosthetic group conjugates, and directly labelled peptide/antibodies
allow for PET imaging of a wide variety of molecular processes. limitations on the application of
124
I for PET imaging is
essentially to the limits of the imagination of the radiochemist, with the feasibility of non-radioactive 'cold' precursor syn-
thesis and/or radioiodination conditions being the major hurdle. similarly to
18
F radiochemistry, and in stark contrast to
radiometal chemistry,
124
I is optimally suited to 'stealth' substitution of hydrogen atoms on pre-existing drugs with known
biological activity. In this way, the native functions and pharmacology of these drugs can be explored using PET imaging in
a manner that is not possible with the attachment of bulky radiometallated chelator complexes or prosthetic groups. The
100.2-hour half-life of
124
I allows for imaging 3+ days post-injection of biovectors with long biological half-lives such as
antibodies; however, the high-energy γ emission of
124
I would expose patients to significant absorbed doses. One major lim-
itation for the expansion of
124
I use in radiopharmaceuticals is its limited production and availability; however, new produc-
tion methods and increasing availability of small biomedical cyclotrons is alleviating this problem [27]. The more lengthy
and challenging radiosynthetic protocols required for producing radiohalogen-containing tracers is also in stark contrast to
the simple and facile kit-preparation deployment of radiometal-containing agents. Both modalities have strengths and weak-
nesses, and when deployed for the right applications they provide very powerful molecular imaging tools.
5.9
conclusIons
Each of the five inorganic PET nuclides discussed in this chapter have unique characteristics that can be both positive and
negative, depending on the application. One fact that should stand out is that there are no universally applicable BFC sys-
tems, because each radiometal has unique chemical and nuclear properties that require careful matching with the desired
BFC-conjugate and the targeted biological process. A single chelator/BFC cannot satisfy the unique coordination chem-
istry of every radiometal ion discussed here, thus the modularity of BFC systems must be exploited to properly tailor the
BFC to match each isotope and application. Many nuclides are used in conjunction with others as matched isotope pairs
for use in theranostic radiopharmaceuticals, so decay properties such as half-lives and emission types (PET/sPECT/
therapy) must be carefully matched to optimise bioequivalence and subsequently maximise the accuracy of imaging/
dosimetry. In contrast to bulky BFC-based radiometal-biovector conjugates, radiohalogens such as radioiodine present the
opportunity for 'stealth' hydrogen atom substitution (often aromatic hydrogens) in small molecule agents, which can pro-
vide pharmacological and imaging data on the small molecule's native biological functions and metabolism. like most
disciplines, there exists no 'magic-bullet' radiopharmaceutical. Many different nuclides must be evaluated so that a variety
of tools are available for radiochemists and nuclear medicine practitioners to study and apply to a vast number of
biochemical processes and disease states.
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