Abstract
Aim/Introduction: Targeted radionuclide therapy (TRT) with lutetium-177 labelled molecules has proven to be effective for the treatment of several malignancies. This includes radiopharmaceuticals targeting the gastrin releasing peptide receptor (GRPR), e.g. [177Lu]Lu-NeoB, which is currently in clinical trials for treatment of GRPR-expressing cancers such as breast cancer (BCa) and prostate cancer (PCa). Due to the growing demand of lutetium-177 for TRT, as well as the aim to further improve the efficacy of the therapy, alternative radionuclides
are being explored. A promising radionuclide is terbium-161; this radionuclide emits β- radiation similar to lutetium-177, while also emitting auger electrons.Accordingly, we aimed to compare [161Tb]Tb-NeoB and [177Lu]Lu-NeoB for targeting GRPR expressing cancers.
Materials and Methods: The binding affinity of both [161Tb]Tb-NeoB or [177Lu]Lu-NeoB was assessed by performing an in vitro autoradiography on frozen GRPR-positive human BCa sections (n=3). Tissue slices were incubated with 1nM [161Tb]Tb-NeoB or [177Lu]Lu-NeoB (+/- 1 µM unlabelled NeoB) for 1 hour, exposed to phosphor screens, and read using a Cyclone phosphor imager. Binding of the radiopharmaceuticals was expressed as percentage added dose/mm2 (%AD/mm2) by normalizing the data to standards. Additionally, the uptake of [161Tb]Tb-NeoB and [177Lu]Lu-NeoB was determined in a human GRPR-expressing PCa cell line PC3-PIP. Cells were incubated with 1nM [161Tb]Tb-NeoB or [177Lu]Lu-NeoB (+/- 1 µM unlabelled NeoB) for 1 hour and cellular uptake was determined using a γ-counter, expressed as percentage added dose/200.000 cells (%AD/200.000 cells). Results: In vitro autoradiography revealed an overall slightly lower binding affinity of [161Tb]Tb-NeoB compared to [177Lu]Lu-NeoB in the same tissue sections, with respective values ranging from 0.020-0.11 %AD/mm2 vs. 0.013-0.15 %AD/mm2. Similarly, the specific uptake of [161Tb]Tb-NeoB was slightly lower but within the same range as that of [177Lu]Lu-NeoB, i.e. 9.16±0.61 vs. 12.02±0.41 %AD/200.000 cells, respectively.
Conclusion: Our studies demonstrate that the binding affinity and specific cellular uptake of [161Tb]Tb-NeoB is slightly lower but still within the same range as that of [177Lu]Lu-NeoB. We have previously observed similar slightly lower specific uptake of terbium-161 labelled compounds directed to different targets,
with a yet unknown underlying cause. Further assessment of the cytotoxic effects of [161Tb]Tb-NeoB in comparison to [177Lu]Lu-NeoB are currently ongoing. So far, our observations support the idea that terbium-161 can be a good alternative to lutetium-177 for GRPR-mediated TRT. Our future studies will reveal whether the auger electrons emitted by terbium-161 will benefit GRPR-mediated TRT.
are being explored. A promising radionuclide is terbium-161; this radionuclide emits β- radiation similar to lutetium-177, while also emitting auger electrons.Accordingly, we aimed to compare [161Tb]Tb-NeoB and [177Lu]Lu-NeoB for targeting GRPR expressing cancers.
Materials and Methods: The binding affinity of both [161Tb]Tb-NeoB or [177Lu]Lu-NeoB was assessed by performing an in vitro autoradiography on frozen GRPR-positive human BCa sections (n=3). Tissue slices were incubated with 1nM [161Tb]Tb-NeoB or [177Lu]Lu-NeoB (+/- 1 µM unlabelled NeoB) for 1 hour, exposed to phosphor screens, and read using a Cyclone phosphor imager. Binding of the radiopharmaceuticals was expressed as percentage added dose/mm2 (%AD/mm2) by normalizing the data to standards. Additionally, the uptake of [161Tb]Tb-NeoB and [177Lu]Lu-NeoB was determined in a human GRPR-expressing PCa cell line PC3-PIP. Cells were incubated with 1nM [161Tb]Tb-NeoB or [177Lu]Lu-NeoB (+/- 1 µM unlabelled NeoB) for 1 hour and cellular uptake was determined using a γ-counter, expressed as percentage added dose/200.000 cells (%AD/200.000 cells). Results: In vitro autoradiography revealed an overall slightly lower binding affinity of [161Tb]Tb-NeoB compared to [177Lu]Lu-NeoB in the same tissue sections, with respective values ranging from 0.020-0.11 %AD/mm2 vs. 0.013-0.15 %AD/mm2. Similarly, the specific uptake of [161Tb]Tb-NeoB was slightly lower but within the same range as that of [177Lu]Lu-NeoB, i.e. 9.16±0.61 vs. 12.02±0.41 %AD/200.000 cells, respectively.
Conclusion: Our studies demonstrate that the binding affinity and specific cellular uptake of [161Tb]Tb-NeoB is slightly lower but still within the same range as that of [177Lu]Lu-NeoB. We have previously observed similar slightly lower specific uptake of terbium-161 labelled compounds directed to different targets,
with a yet unknown underlying cause. Further assessment of the cytotoxic effects of [161Tb]Tb-NeoB in comparison to [177Lu]Lu-NeoB are currently ongoing. So far, our observations support the idea that terbium-161 can be a good alternative to lutetium-177 for GRPR-mediated TRT. Our future studies will reveal whether the auger electrons emitted by terbium-161 will benefit GRPR-mediated TRT.
| Original language | English |
|---|---|
| Article number | OP-668 |
| Pages (from-to) | S319 |
| Number of pages | 1 |
| Journal | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume | 51 |
| Issue number | Suppl 1 |
| DOIs | |
| Publication status | Published - 27 Sept 2024 |
