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

Theranostic Radiopharmaceutical-Guided Robotic Surgery for Precision Tumor Resection and Targeted Elimination of Residual Disease in Digestive System Malignancies. (PubMed, Cancer Biother Radiopharm) - "This FAP-targeted perioperative theranostic strategy was feasible and showed promising imaging, surgical, therapeutic, and safety performance in digestive system malignancies."

Journal • Gastrointestinal Disorder • Oncology • Pancreatic Cancer

Translational Theranostics in Glioblastoma: FAPI-46 as a Precision Medicine Tool. (PubMed, J Nucl Med) - "[177Lu]Lu-FAPI-46 demonstrated lower therapeutic efficacy, as a monotherapy or in combination with temozolomide, than did [225Ac]Ac-FAPI-46. FAPI-46 demonstrates significant potential as a theranostic agent for glioblastoma in peripheral models. However, its inability to cross the blood-brain barrier in orthotopic models highlights the need for future studies to improve its clinical applicability."

Journal • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor • FAP

Prolonging the Therapeutic Window with Fe²⁺-Reactive Small-Molecule Radioligands (SNMMI 2026) - "Info Purpose/Background: With the recent FDA approvals of Pluvicto and Lutathera, there is increasing enthusiasm for the development of radioligand therapies to treat aggressive cancers...Efficacy study indicated administration of two rounds of 177Lu-FAPI-TRX treatment produced significant inhibition of tumor growth and improvement in survival relative to 177Lu-FAPI-46 and saline control... A series of ligand–trioxolane conjugates were successfully synthesized and labeled with ⁶⁴Cu, enabling improved tumor uptake and tumor-to-background contrast across FAP, αvβ3, and uPAR targeting systems in PET/CT. Building on these results, the FAPI–TRX was further labeled with ¹⁷⁷Lu to assess its therapeutic potential. In dosing studies, two administrations of ¹⁷⁷Lu–FAPI–TRX produced a pronounced suppression of tumor growth."

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 Evaluation of [68Ga]Ga-FAPI-A1 as a Novel Radiotracer Targeting Fibroblast Activation Protein. (PubMed, Mol Pharm) - "For therapeutic evaluation, we compared the tumor growth inhibition effects of [177Lu]Lu-FAPI-A1 and [177Lu]Lu-FAPI-46...Clinical uptake of [68Ga]Ga-FAPI-A1 mirrored that of FAPI-46. FAPI-A1 exhibits enhanced binding affinity, which improves tumor uptake and prolongs the retention of [177Lu]Lu-FAPI-A1, supporting its theranostic potential."

Journal • Oncology

FAPI-Based Theranostics in Medullary Thyroid Cancer: A Viable Alternative When Somatostatin Receptor Based Theranostics Show Limited Efficacy—A Clinical Experience (EANM 2025) - "A few months later, the patient developed cough, prompting a 99m Tc-octreotide scan ( A ) as a prerequisite for peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE...[4–6] Cancer-associated fibroblasts (CAFs) have been extensively studied across various cancer types, underscoring their significant role within the tumor microenvironment.[7–10] The targeting of CAFs with FAPI is poised to address gaps in efficacy observed with other theranostic agents.[7,11,12] While octreotide remains the most widely utilized tracer for tumors expressing somatostatin receptors (SSTR), FAPI has occasionally demonstrated superior performance in imaging compared to SSTR-based methods.[13] MTC, a C-cell neuroendocrine neoplasm, has shown promising outcomes with the use of 99m Tc-FAPI-46 [2], 68 Ga-FAPI-46 [2,14] and 68 Ga-FAPI-04 [15–17] for diagnostic imaging, as well as 177 Lu-FAPI-46 [14] and 177 Lu-DOTAGA (SA.FAPI) 2 [1] for theranostic applications...However, our patient..."

Clinical • Cough • Endocrine Cancer • Hepatocellular Cancer • Hepatology • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Respiratory Diseases • Solid Tumor • Thrombosis • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • CAFs • SSTR

Impact of Albumin-Binding Moieties on Structure-Affinity-Pharmacokinetic Relationships of Novel FAP-Targeting Radioligands. (PubMed, Mol Pharm) - "While [68Ga]Ga-FAPI-46 is a promising FAP-targeting radioligand for cancer diagnosis, clinical application of [177Lu]Lu-FAPI-46 for targeted radionuclide therapy is limited due to its insufficient tumor retention...Moreover, the difference in ALB moieties of 111In-labeled compounds influenced their tumor accumulation properties, with [111In]In-FAPI-46-I demonstrating the highest tumor accumulation. These results suggest that the pharmacokinetics of [111In]In-FAPI-46 are modified by ALB moieties, and that [111In]In-FAPI-46-I may be a promising FAP-targeting radioligand."

Journal • PK/PD data • Oncology

The Impact of Dosimetry Extrapolation Methods for Theranostic Applications of Fibrosing Mediastinitis. (PubMed, Mol Pharm) - "Extrapolated absorbed dose estimates suggest that a uterine dose of 16 Gy could be reached with an administered activity of less than 2.78 GBq, depending on the dosimetry model used. These findings highlight the necessity of careful dose planning and special consideration for protecting reproductive organs, particularly in younger female patients, during future clinical trials of 177Lu-FAPI-46 for FM."

Journal • Fibrosis

Exploration of the utilization of irreversible cysteine protease inhibitor in FAP-targeted radiopharmaceuticals design to increase tumor residence time. (PubMed, Nucl Med Biol) - "[177Lu]Lu-FAPI-ET1 demonstrates that the endolysosomal trapping approach can be successfully implemented in FAP-targeted agents and achieve enhanced FAP-positive U-87MG tumor residualization. Although the decreased internalization rate and in vivo targeting of [177Lu]Lu-FAPI-ET1 compared to [177Lu]Lu-FAPI-46 and the ambiguity concerning FAP-mediated internalization efficacy due to targeting vector adduct formation are hurdles to the current implementation. Future approaches are focused on better characterizing FAP adduct formation and cellular trafficking to reveal new pathways to optimize the endolysosomal trapping approach for FAP-targeted agents."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CTSB • CTSS • 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."

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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