TY - JOUR

T1 - Combination of [177Lu]Lu-DOTA-TATE Targeted Radionuclide Therapy and Photothermal Therapy as a Promising Approach for Cancer Treatment

T2 - In Vivo Studies in a Human Xenograft Mouse Model

AU - Simón, Marina

AU - Jørgensen, Jesper Tranekjær

AU - Khare, Harshvardhan A.

AU - Christensen, Camilla

AU - Nielsen, Carsten Haagen

AU - Kjaer, Andreas

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - Peptide receptor radionuclide therapy (PRRT) relies on α-and β-emitting radionuclides bound to a peptide that commonly targets somatostatin receptors (SSTRs) for the localized killing of tumors through ionizing radiation. A Lutetium-177 (177Lu)-based probe linked to the somatostatin analog octreotate ([177Lu]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 [177Lu]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 [177Lu]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.

AB - Peptide receptor radionuclide therapy (PRRT) relies on α-and β-emitting radionuclides bound to a peptide that commonly targets somatostatin receptors (SSTRs) for the localized killing of tumors through ionizing radiation. A Lutetium-177 (177Lu)-based probe linked to the somatostatin analog octreotate ([177Lu]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 [177Lu]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 [177Lu]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.

KW - cancer

KW - nanoshells (NS)

KW - peptide receptor radionuclide therapy (PRRT)

KW - photothermal therapy (PTT)

KW - somatostatin receptor (SSTR)

KW - [177Lu]Lu-DOTA-TATE

UR - http://www.scopus.com/inward/record.url?scp=85132576048&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics14061284

DO - 10.3390/pharmaceutics14061284

M3 - Journal article

C2 - 35745856

AN - SCOPUS:85132576048

VL - 14

SP - 1

EP - 16

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 6

M1 - 1284

ER -