Panel Disdussion

3rd International Congress 3rd International of Nuclear Congress Medicine of Nuclear & 15th Medicine Iranian Annual & 15th Iranian Congress Annual of
Nuclear Congress Medicine of Nuclear Medicine
Shahid Beheshti Shahid Beheshti University University of Medical Sciences of Medical 19-21 Sciences May 201119-21 May 2011
Peptides based radiopharmaceuticals for Tumor Diagnosis and
Therapy
Mostafa Erfani (Iran)
Nuclear Science Research School, Nuclear Science & Technology Research
Institute (NSTRI), Atomic Energy Organization of Iran
The specific binding of peptides to their receptors can be used to
meet the key requirement in tumor targeting. Because of their small
size, peptides exhibit faster blood clearance and higher target-tobackground
ratios compared to macromolecular compounds.
Although the use of an 111 In peptide was first explored for the use in
nuclear medicine in 1981, it was not until a decade later that a 123 I
labelled peptide was injected to tumor bearing animals. To date,
radiolabelled receptor-binding peptides have emerged as a new class
of radiopharmaceuticals. There is a tremendous amount of peptides
that are potential candidates for being used as tumor imaging
radiopharmaceuticals. For example octereotide, bombesin, gastrins,
angiotansin, RGD, substance p, NPY are examples that are currently
being tested, and many more have been suggested.
There are several prerequisites for peptides used for scintigraphy or
even radio-therapy. First of all, the corresponding receptors have to
be expressed on the target in suitable amounts, over expression is
desirable. There is no sense in developing a radioligand for a clinically
important disease if the receptor is not concentrated in the target
tissue in such an amount that an external image can be obtained.
Natural peptide ligands exhibit high affinity to the receptor, usually in
the nano molar range. It is crucial that the radiolabeled analog
retains its high affinity. Because of the small size of peptides, the
attachment of a bulky chelator and a radionuclide has a significant
contribution the overall molecular weight, which may lead to
conformational changes in the binding sequence. Thus, the
attachment of the radiolabel should be made far from the receptor
binding sequence, or a spacer should be introduced. Specificity is also
a prerequisite. Whereas the natural ligand usually binds with similar
affinities to receptor subtypes, chemically modified synthetic
analogues often display pronounced subtype selectivity for only one
or few receptor subtypes. Thus, receptor subtype expression on the
targeted tumor tissue has to be considered. Receptor-agonists are
preferred, since they usually exhibit receptor-mediated
internalization. This results in accumulation of the radioligand in the
target, providing an increased signal for scintigraphy. For therapeutic
applications, internalization is an absolute precondition, as the
cytotoxic moiety has to reach its target within the cell. A further
prerequisite for radiopeptides is that the complexing of the chelatorpeptide
with the radiometal is achieved in high yields. Last, but not
least, a main concern of radiolabelled peptides is their stability under
physiological conditions, i.e. peptide fragmentation by peptidases and
the stability of the radiometal-chelator complex.
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