[177Lu]FAPI-46 / Novartis - LARVOL DELTA

Biodistribution and dosimetry of FAPI-46 in mouse model of colorectal carcinoma with PET and SPECT imaging (AACR 2025) - "Animals were dosed with 177Lu-FAPI-46 or 68Ga-FAPI-46, scanned with SPECT (Mediso) or PET (Sedecal) up to 90 minutes...FAPI is suitable for multipurpose imaging and there is a great interest towards this molecule in the fields of imaging and oncology. The same precursor structure can be labeled with more than one radionuclide with high radiochemical yield and purity."

Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • FAP

Development and Application of Radioactive Ligands Targeting Fibroblasts with Albumin-Binding Sites. (PubMed, Mol Cancer Ther) - "177Lu-DOTA-ALB-02 has longer retention in circulation than 177Lu-FAPI-46 and other radioligands...Notably, 177Lu-DOTA-ALB-02 had a significant tumor/ nontarget (T/NT) ratio as indicated by biodistribution data. The outstanding tumor retention properties of 177Lu-DOTA-ALB-02 have been demonstrated in small animal single photon emission computed tomography (micro-SPECT) imaging and biodistribution studies, therefore it is considered the albumin-binding FAPI with the most favorable pharmacokinetic and imaging properties, worthy of further clinical investigation."

Journal • Oncology

Significant 99mTc-FAPI-46 Uptake in 2 Cases of TENIS Syndrome With Negative Tc-OCTREOTIDE Scan, a New Hope in Theranostic Applications. (PubMed, Clin Nucl Med) - "Malignant FAPI uptake was evident in the lungs, liver, adrenal, and abdominal lymph nodes in a patient and in the lungs of another one. Due to proper uptake in diagnostic scans, these patients were recognized as a suitable candidate for treatment with 177Lu-FAPI-46."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Enhanced Diagnostic and Therapeutic Potentials of 68Ga-LNC1013 and 177Lu-LNC1013 in Cancer Imaging and Radionuclide Therapy: A Comparative and Preclinical Study (EANM 2024) - "This tracer demonstrated superior tumor growth inhibition compared to 177Lu-FAPI-46 and control groups in CDXs, suggesting effective radionuclide therapy potential. 68Ga-LNC1013 outperforms 18F-FDG in the diagnostic imaging of diverse cancer types, providing higher contrast and detection sensitivity. The theranostic potential of this tracer series is further highlighted by the promising therapeutic outcomes of 177Lu-LNC1013 in preclinical models, setting the stage for advanced FAP-targeted theranostics in oncology."

Preclinical • Oncology

In vitro and in vivo analyses of eFAP: a novel FAP-targeting small molecule for radionuclide theranostics and other oncological interventions. (PubMed, EJNMMI Radiopharm Chem) - "The superior affinity and faster tumor accumulation of eFAP-6 over FAPI-46 makes it a suitable compound for radionuclide imaging. After further optimization, the eFAP series has great potential for various oncological interventions, including fluorescent-guided surgery and effective targeted radionuclide theranostics."

Journal • Preclinical • Oncology • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013 (SNMMI 2024) - "The lead compound, 68Ga -LNC1013, was then labeled with 177Lu in a biodistribution study against the FAPI monomer, 177Lu-FAPI-46, measured with a γ-counter. Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over their monomeric counterparts. We demonstrated that LNC1013, the lead compound without piperazine moiety, had superior diagnostic potential when labeled with 68Ga over 68Ga-FAPI-46 and 18F-FDG. A preliminary experiment with 177Lu suggests extended retention of dimer in HT-1080 tumor-bearing mice model and implies its potential for radioligand therapy of FAP-positive cancers."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Solid Tumor • FAP

The Synergy of 177Lu-FAPI-046 with Tyrosine Kinase Inhibitor in a Sarcoma Patient-Derived Xenograft Mouse Model. (PubMed, Biomed J) - "This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of 177Lu-FAPI-46 with Pazopanib."

Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CASP3 • FAP

Comparative biodistribution and radiotherapeutic efficacy of the fibroblast activation protein (FAP)-targeting agents FAP-2286 and FAPI-46 (AACR 2022) - P1/2 | "In preclinical studies, the radiotherapeutic 177Lu-FAP-2286 showed longer tumor retention, resulting in greater tumor inhibition than 177Lu-FAPI-46. The phase 1/2 LuMIERE clinical trial (NCT04939610) will evaluate FAP-2286 as a therapeutic (177Lu-FAP-2286) and imaging (68Ga-FAP-2286) agent in multiple indications."

Clinical • Oncology • FAP

Anti-PSMA antibody radiolabeled with 177Lu improves MFS in high-risk nmCRPC (YouTube) - "Prof Tagawa outlines that the results showed anti-PSMA mAb J591 with ketoconazole/ hydrocortisone when radiolabelled with 177Lu lead to improved 18-month metastasis-free survival versus 111In."

Video

Fibroblast Activation Protein specific PET/CT imaging in fibrotic interstitial lung diseases and lung cancer: a translational exploratory study. (PubMed, J Nucl Med) - "Patients and PET-Scans of 15 patients with fILD and suspected LC were acquired 10, 60 and 180 minutes after the administration of 150-250 MBq of a Ga labelled FAPI tracer (FAPI-46)... FAPI-PET/CT imaging is a promising new imaging modality for fILD and LC. Its potential clinical value for monitoring and therapy evaluation of fILD should be investigated in future studies."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • Solid Tumor • FAP

Fibroblast activation protein targeted therapy using [Lu]FAPI-46 compared with [Ac]FAPI-46 in a pancreatic cancer model. (PubMed, Eur J Nucl Med Mol Imaging) - "This study suggested the possible application of FAPI radioligand therapy in FAP-expressing pancreatic cancer. Further evaluation is necessary to find the best radionuclide with shorter half-life, as well as the combination with therapies targeting tumour cells directly."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • FAP

Initial clinical experience with Y-FAPI-46 radioligand therapy for advanced stage solid tumors: a case series of nine patients. (PubMed, J Nucl Med) - "Low radiation doses to organs at risk suggest feasibility of repeat cycles of Y-FAPI-46. We observe signs of clinical activity, but further studies are warranted to determine efficacy and toxicity profile in a larger cohort."

Clinical • Journal • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Thrombocytopenia • FAP

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177Lu-FAPI-46. (PubMed, Clin Nucl Med) - "Follow-up examinations after 4 cycles of 177Lu-FAPI-46 treatment revealed stable metastatic lesions, resulting in stable disease. This case demonstrated the potential feasibility of 177Lu-FAPI-46 in the treatment of advanced RAIR-DTC; further research on improving the FAP-targeting vector may be necessary."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Correlation of Ga-FAPi-46 PET biodistribution with FAP expression by immunohistochemistry in patients with solid cancers: a prospective translational exploratory study. (PubMed, J Nucl Med) - " In this interim analysis of a prospective exploratory imaging trial, Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlated with FAP tissue expression. These findings support further exploration of FAPi PET as a pan-cancer imaging biomarker for FAP expression and stratification tool for FAP- targeted therapies."

Clinical • Journal • Biliary Cancer • Oncology • Solid Tumor • FAP

Administration routes for SSTR- / PSMA- and FAP-directed theranostic radioligands in mice. (PubMed, J Nucl Med) - " Healthy and tumor-bearing male C57BL/6 or NOD SCID Gamma mice, respectively, were applied with a mean of 6.0±0.5 MBq Ga DOTATOC (RM1-SSTR allograft), 5.3±0.3 MBq Ga-PSMA11 (RM1-PSMA allograft) or 4.8±0.2 MBq Ga-FAPI46 (HT1080 FAP xenograft) i.v., i.p., s.c. or p.o...S.c. administration resulted in highest absolute SSTR tumor and tumor-to-organ uptake as compared to the i.v. route, warranting further clinical assessment."

Journal • Preclinical • Oncology • FAP • SSTR

FAP-targeted radionuclide therapy with [Lu]Lu-FAPI-46 in metastatic nasopharyngeal carcinoma. (PubMed, Eur J Nucl Med Mol Imaging) - No abstract available

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Head-to-head comparison of Ga-FAPI-46 and F-FDG PET/CT for evaluation of head and neck squamous cell carcinoma: a single-center exploratory study. (PubMed, J Nucl Med) - "FTV was greater than MTV (P < 0.05), but no significant differences were observed for the other parameters. Ga-FAPI-46 PET/CT showed good concordance and comparable diagnostic performance compared with F-FDG PET/CT for initial staging and recurrence detection in patients with HNSCC."

Clinical • Head-to-Head • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • FAP • FDG PET

SOFIE gets greenlight from U.S. FDA to proceed to Phase II Pancreatic Cancer Study (PRNewswire) - "SOFIE Biosciences...has received clearance to proceed with its Fibroblast Activation Protein Inhibitor (FAPI) clinical trial after completing a 30-day IND review with the FDA. The IND is for a Phase 2, Multicenter, Single Blind, Non-randomized Study of [68Ga]FAPI-46 PET for imaging patients with Pancreatic Ductal Adenocarcinoma (PDAC)."

IND • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer. (PubMed, Radiology) - "Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (Ga)-FAPI-46.."

Journal • Breast Cancer • Oncology • Solid Tumor • FAP • MRI

Pitfalls and common findings in Ga-FAPI-PET - A pictorial analysis. (PubMed, J Nucl Med) - "Methods and materials: 91 patients underwent whole-body PET/CT with either FAPI-04 (N = 25) or FAPI-46 (N = 66)... Pitfalls include non-tumor specific Ga-68-FAPI uptake in degenerative lesions, muscle, head-and-neck, scarring, mammary glands or uterus. Here we summarize findings to inform readers at centers introducing Ga-68-FAPI-PET to avoid common mistakes."

Journal • Oncology • FAP

SOFIE Submits Investigational New Drug Application to US FDA for Pancreatic Cancer Imaging (PRNewswire) - "SOFIE Biosciences...achieves a major milestone with the filing of an IND application to the FDA for a radiopharmaceutical targeting Fibroblast Activation Protein Inhibitor (FAPI). The IND is for a Phase 2, Multicenter, Single Blind, Non-randomized Study of [68Ga]FAPI-46 PET for imaging patients with Pancreatic Ductal Adenocarcinoma (PDAC). This filing, which continues the progress of SOFIE's Global Academic Probe Network, allows select institutions to participate with the Company in generating clinically relevant diagnostic imaging data to support ongoing work in this critical oncologic indication, pancreatic cancer, and numerous other solid tumors and non-oncologic applications."

IND • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Novel Theranostic Approach to Sarcomas: Insights into the Diagnostic and Therapeutic Use of FAP Radioligands (DGHO 2021) - "FAPI-PET is a valuable diagnostic tool in patients with sarcoma. We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. We further demonstrate high accuracy of FAPI-PET and, when compared to FDG-PET, similarly high detection rate and reproducibility."

Hematological Disorders • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Thrombocytopenia • FAP • FDG PET