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Design, Preclinical Evaluation, and Clinical Translation of 68 Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma.
- Source :
-
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Mar 01; Vol. 65 (3), pp. 394-401. Date of Electronic Publication: 2024 Mar 01. - Publication Year :
- 2024
-
Abstract
- Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH <subscript>2</subscript> (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with <superscript>68</superscript> Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with <superscript>68</superscript> Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of <superscript>68</superscript> Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of <superscript>18</superscript> F-FDG. Results: <superscript>68</superscript> Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of <superscript>68</superscript> Ga-FAPI-LM3 was significantly higher than that of <superscript>68</superscript> Ga-FAPI-46 and <superscript>68</superscript> Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, <superscript>68</superscript> Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did <superscript>18</superscript> F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: <superscript>68</superscript> Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric <superscript>68</superscript> Ga-FAPI and <superscript>68</superscript> Ga-DOTA-LM3. This study highlights the clinical feasibility of <superscript>68</superscript> Ga-FAPI-LM3 PET/CT for NPC imaging.<br /> (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Details
- Language :
- English
- ISSN :
- 1535-5667
- Volume :
- 65
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38176714
- Full Text :
- https://doi.org/10.2967/jnumed.123.266183