Design, Preclinical Evaluation, and Clinical Translation of⁶⁸Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma

Abstract

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Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET

“…This possibility suggests the need for further research to assess the effectiveness of various imaging probes in detecting pulmonary fibrosis, potentially expanding the available diagnostic tools for this disease. Our previous study confirmed the dual-targeting capability of FAPI-LM3 against FAP and SSTR2 in tumor tissues, 12 demonstrating their enhanced uptake and prolonged retention in nasopharyngeal carcinoma (showing positive FAP and SSTR2 expression). This groundwork set the stage for potential future applications in radionuclide internal irradiation therapy for advanced nasopharyngeal carcinoma using 177 Lulabeled compounds.…”

“…For heterobivalent probes to be effective, it is crucial that each binding motif retains its biological activity, utilizing a multivalent effect to enhance receptor availability and consequently fibrotic lesion uptake. , This strategy highlights the superiority of heterobivalent molecules over their monomeric counterparts. Various small heterobivalent molecules, including FAPI-PSMA, FAPI-RGD, and BBN-PSMA, exhibit increased tracer uptake in tumors, demonstrating the effectiveness of the dual-targeting approach. ,, Moreover, considering the association of integrin α v β 3 with pulmonary fibrosis, other heterobivalent probes such as FAPI-RGD, which targets integrin α v β 3 and FAP, could potentially detect pulmonary fibrosis. This possibility suggests the need for further research to assess the effectiveness of various imaging probes in detecting pulmonary fibrosis, potentially expanding the available diagnostic tools for this disease.…”

“…In nuclear medicine, radiolabeled target-specific molecular probes offer a powerful tool for real-time visualization of lesions. Building on our previous research, we developed a novel heterobivalent molecule that targets both FAP and SSTR2, denoted as FAPI-LM3, for PET imaging of nasopharyngeal carcinoma (NPC) . This heterobivalent molecule specifically targets both FAP and SSTR2, making it particularly effective for the detection and staging in patients with NPC .…”

“…Building on our previous research, we developed a novel heterobivalent molecule that targets both FAP and SSTR2, denoted as FAPI-LM3, for PET imaging of nasopharyngeal carcinoma (NPC). 12 This heterobivalent molecule specifically targets both FAP and SSTR2, making it particularly effective for the detection and staging in patients with NPC. 12 To address the clinical challenge of early and accurate diagnosis of pulmonary fibrosis, we aimed to investigate the potential of 68 Ga radiolabeled FAPI-LM3 as a functional imaging modality for the quantitative evaluation of pulmonary fibrotic changes.…”

“…12 This heterobivalent molecule specifically targets both FAP and SSTR2, making it particularly effective for the detection and staging in patients with NPC. 12 To address the clinical challenge of early and accurate diagnosis of pulmonary fibrosis, we aimed to investigate the potential of 68 Ga radiolabeled FAPI-LM3 as a functional imaging modality for the quantitative evaluation of pulmonary fibrotic changes. By leveraging the dual-targeting capability of 68 Ga-FAPI-LM3, we hypothesized that it could effectively illuminate early stage pulmonary fibrosis lesions, thus advancing noninvasive diagnostic methodologies for this debilitating condition.…”