Journal
PHARMACEUTICS
Volume 14, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14061284
Keywords
photothermal therapy (PTT); nanoshells (NS); peptide receptor radionuclide therapy (PRRT); [Lu-177]Lu-DOTA-TATE; somatostatin receptor (SSTR); cancer
Categories
Funding
- European Union's Horizon 2020 research and innovation programme [670261, 668532]
- Lundbeck Foundation
- Novo Nordisk Foundation
- Innovation Fund Denmark
- Neuroendocrine Tumor Research Foundation
- Danish Cancer Society
- Arvid Nilsson Foundation
- Neye Foundation
- Research Foundation of Rigshospitalet
- Danish National Research Foundation [126]
- Research Council of the Capital Region of Denmark
- Danish Health Authority
- John and Birthe Meyer Foundation
- Research Council for Independent Research
- H2020 Societal Challenges Programme [668532] Funding Source: H2020 Societal Challenges Programme
- European Research Council (ERC) [670261] Funding Source: European Research Council (ERC)
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Investigating the combination of [Lu-177]Lu-DOTA-TATE PRRT and nanoshell (NS)-based PTT for treating SSTR-expressing small-cell lung tumors in mice, the study showed improved survival with the combination treatment compared to PRRT alone, highlighting the importance of treatment timing. The combination treatment was well-tolerated in the mice, suggesting the potential of NS-based PTT as an add-on to PRRT for further investigation.
Peptide receptor radionuclide therapy (PRRT) relies on alpha- and beta-emitting radionuclides bound to a peptide that commonly targets somatostatin receptors (SSTRs) for the localized killing of tumors through ionizing radiation. A Lutetium-177 (Lu-177)-based probe linked to the somatostatin analog octreotate ([Lu-177]Lu-DOTA-TATE) is approved for the treatment of certain SSTR-expressing tumors and has been shown to improve survival. However, a limiting factor of PRRT is the potential toxicity derived from the high doses needed to kill the tumor. This could be circumvented by combining PRRT with other treatments for an enhanced anti-tumor effect. Photothermal therapy (PTT) relies on nanoparticle-induced hyperthermia for cancer treatment and could be a useful add-on to PRRT. Here, we investigate a strategy combining [Lu-177]Lu-DOTA-TATE PRRT and nanoshell (NS)-based PTT for the treatment of SSTR-expressing small-cell lung tumors in mice. Our results showed that the combination treatment improved survival compared to PRRT alone, but only when PTT was performed one day after [Lu-177]Lu-DOTA-TATE injection (one of the timepoints examined), showcasing the effect of treatment timing in relation to outcome. Furthermore, the combination treatment was well-tolerated in the mice. This indicates that strategies involving NS-based PTT as an add-on to PRRT could be promising and should be investigated further.
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