Bibliographic Details
| Title: |
In vitro and ex vivo evaluation of preclinical models for FAP-targeted theranostics: differences and relevance for radiotracer evaluation |
| Authors: |
Circe D. van der Heide, Joana D. Campeiro, Eline A. M. Ruigrok, Lilian van den Brink, Shashikanth Ponnala, Shawn M. Hillier, Simone U. Dalm |
| Source: |
EJNMMI Research, Vol 14, Iss 1, Pp 1-13 (2024) |
| Publisher Information: |
SpringerOpen, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Medical physics. Medical radiology. Nuclear medicine |
| Subject Terms: |
Cancer-associated fibroblast (CAF), Fibroblast activation protein (FAP), Targeted radionuclide therapy (TRT), Radionuclide theranostics, Preclinical models, Medical physics. Medical radiology. Nuclear medicine, R895-920 |
| More Details: |
Abstract Background Fibroblast activation protein (FAP) is an attractive target for cancer theranostics. Although FAP-targeted nuclear imaging demonstrated promising clinical results, only sub-optimal results are reported for targeted radionuclide therapy (TRT). Preclinical research is crucial in selecting promising FAP-targeted radiopharmaceuticals and for obtaining an increased understanding of factors essential for FAP-TRT improvement. FAP is mainly expressed by cancer-associated fibroblasts in the tumor stroma and less on cancer cells themselves. Therefore, other (complex) factors impact FAP-TRT efficacy compared to currently clinically applied TRT strategies. For accurate evaluation of these aspects, selection of a representative preclinical model is important. Currently mainly human cancer cell lines transduced to (over)express FAP are applied, lacking clinical representation. It is unclear how these and more physiological FAP-expressing models compare to each other, and whether/how the model influences the study outcome. We aimed to address this by comparing FAP tracer behavior in FAP-transduced HT1080-huFAP and HEK293-huFAP cells, and endogenous FAP-expressing U-87 MG cancer cells and PS-1 pancreatic stellate cells. [111In]In-FAPI-46 and a fluorescent FAP-targeted tracer (RTX-1370S) were used to compare tracer binding/uptake and localization in vitro and ex vivo. Additionally, FAP expression was determined with RT-qPCR and anti-FAP IHC. Results Although FAP expression was highest in HEK293-huFAP cells and cell line derived xenografts, this did not result in the highest tracer uptake. [111In]In-FAPI-46 uptake was highest in HT1080-huFAP, closely followed by HEK293-huFAP, and a 6-10-fold lower uptake for U-87 MG and PS-1 cells. However, ex vivo U-87 MG xenografts only showed a 2-fold lower binding compared to HT1080-huFAP and HEK293-huFAP xenografts, mainly because the cell line attracts murine fibroblasts as demonstrated in our RT-qPCR and IHC studies. Conclusions The interaction between FAP and FAP-targeted tracers differs between models, indicating the need for appropriate model selection and that comparing results across studies using different models is difficult. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2191-219X |
| Relation: |
https://doaj.org/toc/2191-219X |
| DOI: |
10.1186/s13550-024-01191-6 |
| Access URL: |
https://doaj.org/article/3c9a4964d6cd44f694ffdf3cbf59bb8e |
| Accession Number: |
edsdoj.3c9a4964d6cd44f694ffdf3cbf59bb8e |
| Database: |
Directory of Open Access Journals |
