Heterodimer peptide based on RGD and NPY analog for breast tumor targeting
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2023
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INTERNATIONAL SYMPOSIUM ON TRENDS IN RADIOPHARMACEUTICALS
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Resumo
Heterodimer peptides targeting more than one receptor target can be advantageous as tumors can
simultaneously express more than one receptor type. The design of heterodimer peptides can
significantly increase the avidity and specificity of the contrast agent due to simultaneous binding
to more than one type of receptor or at least one receptor independently, compared to their
corresponding monospecific counterparts. A heterodimer molecule consisting of cyclic RGD and
NPY analog motifs in a single probe is an attractive approach, as both receptors are overexpressed
simultaneously in breast cancer. We hypothesize that a peptide ligand recognizing both αvβ3
integrin and NPY receptors will be advantageous because of its dual-receptor-targeting ability,
which could enable the determination of disease location, monitoring of pathological and
molecular changes associated with payload delivery, as well as a comprehensive view of the
material behavior in vivo that can be utilized to guide therapeutic and diagnostic interventions.
The HYNIC-cRGDfk-NPY peptide was radiolabeled with 99mTc using tricine/EDDA as coligand.
The cellular-specific binding of [99mTc]HYNIC-cRGDfk-NPY was evaluated on different
cell lines as well as with a blocking experiment on MCF-7 and MDA-MB231 (human breast cancer
cells). The proof-of-concept of tumor-targeting was performed through ex vivo biodistribution in
normal mice, MCF-7 and MDA-MB231 tumor-bearing mice also in SPECT/CT images. By using
tricine/EDDA as a coligand, labeling yield was more than 97%. The in vitro cell uptake test showed
that this radiolabeled peptide had a good affinity to MDA-MB231 and MCF-7 cells. The in vivo
results showed a tumor/muscle ratio of 5.65 ± 0.94 for MCF-7 model, and 7.78 ± 3.20 for MDAMB231
Also, tumor uptake was reduced significantly from 9.30% to 4.41% (MCF-7) and from
4.93 % to 2.3% (MDA-MB231) in blocking study whereas 500-fold molar excess of cold peptide
was injected 30 min prior to the injection of related radioconjugated peptide suggesting the
potencial of heterobivalent radioligand [99mTc]-HYNIC-cRDGfk-NPY to target breast tumors
targeting.
Como referenciar
FERREIRA, ARYEL. Heterodimer peptide based on RGD and NPY analog for breast tumor targeting. In: INTERNATIONAL SYMPOSIUM ON TRENDS IN RADIOPHARMACEUTICALS, April 17-21, 2023, Vienna, Austria. Abstract... Vienna, Austria: International Atomic Energy Agency - IAEA, 2023. p. 189-189. Disponível em: http://repositorio.ipen.br/handle/123456789/34541. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.