Chemistry Reference
In-Depth Information
the chemIstry of InorganIc nuclIdes
(
86
y,
68
ga,
64
cu,
89
Zr,
124
I)
Eric W. Price and Chris Orvig
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, Vancouver, BC, Canada
5.1
IntroductIon: InorganIc nuclIde-Based radIopharmaceutIcals
The chemistry of molecular imaging agents based on radiometals is intimately tied to several core chemistry disciplines,
such as aqueous metal ion chemistry, coordination chemistry, chelator design/synthesis, and bioconjugation chemistry with
various biomolecular vectors. Biomolecular vectors (biovectors) are biological molecules such as peptides and antibodies
that have high affinity and specificity for specific receptors or tissues. Radiometal-based radiopharmaceuticals have almost
exclusively relied on bifunctional chelators (BFC) as a core to provide site-specific delivery of a tightly bound radioactive
metal ion to biological targets. The targets are specified by a variety of biovectors that can be conjugated (attached) to the
BFC agent. A BFC is simply a chelating agent that possesses the functionality to coordinate both a metal ion and a biovector.
To this end, a successful radiopharmaceutical agent using radiometals must incorporate a high stability chelator with a robust
conjugation site to provide a covalent linkage to an established biovector with high target affinity. The radioactive isotope
used in a radiopharmaceutical is selected based on its decay properties (half-life, emission type and energy, branching ratios)
and is matched with the chelator, biovector, biological target, and purpose of the agent. The radiohalogen
124
I is not utilised
in the same manner as radiometals and is typically incorporated into radiopharmaceutical agents using direct covalent link-
ages, often replacing a hydrogen atom. The chemistry of radioiodine isotopes is very similar to non-radioactive iodine
chemistry.
The chemistry of radioactive “hot” metal ions is identical to regular non-radioactive “cold” metal ions; however, radio-
chemistry is typically performed under extremely dilute conditions. It is also important to note that several of the elements
being discussed have multiple radioactive isotopes that are useful for diagnostic or therapeutic purposes (
86/90
Y,
123/124/125/131
I,
67/68
Ga,
60/61/62/64
Cu), and all isotopes of a given element have identical chemistry [1-6]. A radiopharmaceutical agent based
on one specific isotope will have identical chemistry and biological behaviour when synthesised with any other isotopes of
that same element [1-6]. Assuming that the radioactive decay properties of the other isotopes of the element are useful for
the specific radiopharmaceutical agent in question, substitution is seamless and can yield multiple applications from one
molecular scaffold.
Positron emission tomography (PET) imaging is a very accurate and quantitative imaging technique, so exploration of
positron emitting isotopes is of great significance. The archetypical PET isotope is
18
F, which has a very high positron (β
+
)
abundance of 96% and a low energy β
+
emission of 640 keV (short mean free path from decay location providing high reso-
lution and accuracy). Many of the more exotic PET isotopes discussed here have lower positron abundances (low branching
ratios, ~20-60% decay by β
+
) and higher positron energies, which decreases the accuracy of data collection and requires
longer image acquisition times and/or higher activity injected doses (Table 5.1) [7].
For detection to occur, the positron must be sufficiently slowed down after emission for it to meet an electron and anni-
hilate. The size of the spherical radius that a positron travels from its source is dependent on its energy, and higher energy
