lutetium Lu 177 rofapitide tetraxetan (AAA614) / Clovis, 3B Pharma, Novartis - LARVOL DELTA

Initial Results and Clinical Experiences of [177Lu]Lu-FAP-2286 for Pleural Metastases: A Single-Center Retrospective Study. (PubMed, J Nucl Med) - "This study provides real-world evidence supporting FAP-targeted radiopharmaceutical therapy as a treatment option for this patient population and suggests FAP-based imaging is useful for response monitoring. Larger, prospective studies are warranted to confirm these findings."

Journal • Retrospective data • Hematological Disorders • Oncology • FAP

The Current Status of Radionuclide Tumor Targeting Diagnosis and Therapy Based on FAP-2286: From Preclinical Studies to Clinical Application. (PubMed, Mol Diagn Ther) - "Preclinical and early clinical studies have shown encouraging results, characterized by prolonged in vivo retention and a favorable safety profile, supporting its use as a theranostic agent. This review provides a comprehensive overview of the current literature on FAP-2286, from preclinical development to clinical translation, highlighting its diagnostic value, the status of FAP-targeted radionuclide therapy, and the challenges and opportunities in advancing FAP-based theranostics."

Journal • Preclinical • Review • Oncology

Preclinical Development of 3BP-3940, a Fibroblast Activation Protein-Targeted Cyclic Peptide-Based Radiotheranostic for Imaging and Therapy. (PubMed, J Nucl Med) - "Since the discovery of the FAP inhibitor series, which provided high-contrast images in patients, many radiolabeled FAP-targeting agents have been developed, with the cyclic peptide FAP-2286 currently being the most advanced theranostic compound in clinical development...3BP-3940 showed minimal uptake in normal tissues of mice and minipigs. These findings support the clinical use of 3BP-3940 as a promising FAP-targeting agent for both imaging and radiopharmaceutical therapy in patients with cancer."

Journal • Preclinical • Oncology

Comparative evaluation of [68Ga]Ga-FAP-2286 and [18F]FDG PET/CT in breast cancer and initial experience with [177Lu]Lu-FAP-2286 therapy. (PubMed, Eur J Nucl Med Mol Imaging) - "[68Ga]Ga-FAP-2286 appears to be a promising imaging agent for breast cancer, while [177Lu]Lu-FAP-2286 may represent a potential therapeutic option for patients with advanced disease."

Journal • Breast Cancer • Oncology • Solid Tumor

Radiolabelled FAPI Radiotracers in Oncology: A Comprehensive Review of Current Diagnostic and Emerging Therapeutic Applications. (PubMed, Pharmaceuticals (Basel)) - "Therapeutic evidence shows encouraging tumour retention and safety profiles for agents such as [177Lu]Lu-FAP-2286 and [90Y]Y-FAPI-46, while α-emitting radiotracers (e.g., [225Ac]Ac-FAPI-04) demonstrate potent antitumor effects in preclinical models...Nonetheless, clinical evidence remains in its early stages, and substantial questions persist regarding dosimetry, intertumoral variability in FAP expression, and optimal ligand selection for therapy. Continued development of next-generation FAPI constructs, along with well-designed prospective trials, will be crucial in defining the future role of FAPI-based theranostics in oncology."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • CAFs • FAP

Head-to-head comparison of [177Lu]Lu-FAP-2286 and [161Tb]Tb-FAP-2286 efficacy in a PDAC mouse model. (PubMed, EJNMMI Res) - "In our in vitro and in vivo studies, [177Lu]Lu-FAP-2286 and [161Tb]Tb-FAP-2286 demonstrated similar behavior. In the applied PDAC mouse model, FAP-TRT showed limited therapeutic efficacy, most likely due to the limited radiopharmaceutical uptake observed in the tumors. This hampered determination of a potential benefit of either radioisotope for FAP-TRT. Of note, a modest response was observed in the tandem therapy group that first received [177Lu]Lu-FAP-2286, followed by [161Tb]Tb-FAP-2286."

Head-to-Head • Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • FAP

Non-FDG-Avid pancreatobiliary adenocarcinoma detected by ⁶⁸Ga-FAP-2286 PET/CT. (PubMed, Eur J Nucl Med Mol Imaging) - No abstract available

Journal • Biliary Cancer • Oncology • Pancreatic Cancer

Imaging of Solid Tumors Using FAP-2286 (clinicaltrials.gov) - P1 | N=191 | Recruiting | Sponsor: Thomas Hope | N=131 ➔ 191 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Prostate Cancer • Solid Tumor

Feasibility of albumin binding modulation in FAP-targeting radiopharmaceuticals: insights from molecular docking and experimental analysis. (PubMed, EJNMMI Radiopharm Chem) - "Together, the computational and experimental results underscore the importance of albumin-binding in shaping the pharmacokinetic properties of FAP-targeted radiopharmaceuticals. Strategic optimization of albumin-binding linkers may improve stability, circulation time, and overall therapeutic performance in next-generation FAP-based agents."

Journal

Current status of FAP therapy in solid tumors. (PubMed, Semin Nucl Med) - P3 | "Particularly small molecules (i.e. FAPI-46, FAPI-74) and peptides (i.e. FAP-2286, DOTAGA.SA.FAPi) seem to be some of the most promising molecular probes for imaging and therapy...In contrast, FAP-targeted therapeutics remain in the Phase-I or proof-of-concept stage but brings hope for patients with systemic disease who are left out and urgently need additional innovation drives beyond the standard care. This review article will give insight into the most recent developments in the FAP-Therapeutic applications of cancer treatments using several different promising FAP-derivates to improve FAP-theranostic in oncology."

Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Hepatocellular Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • FAP

177Lu-FAP-2286 Therapy for Advanced Lung Adenocarcinoma With Multiple Metastases: A Promising Last-line Treatment Option. (PubMed, Clin Nucl Med) - "Follow-up 68Ga-FAP-2286 imaging at 2 months demonstrated partial metabolic response (PERCIST 1.0), accompanied by a marked reduction in respiratory tumor marker levels. In addition, no adverse reactions were reported by the patient."

Journal • Cough • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Respiratory Diseases • Solid Tumor

Head-to-head comparison of 18F-FAP-2286 PET/CT and 18F-FDG PET/CT in the diagnosis and staging of clear cell renal cell carcinoma: a prospective study. (PubMed, Eur J Nucl Med Mol Imaging) - No abstract available

Head-to-Head • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Fibroblast activation protein (FAP)-targeted dedicated breast PET for primary invasive lobular carcinoma: A pictorial review (SABCS 2025) - "After undergoing whole-body PET/CT with FAP-targeted radiotracer (6mCi +/-20% of 68Ga-FAP-2286) on a separate research protocol, they underwent dedicated breast imaging using the MAMMI dbPET scanner (OncoVision, Spain) without additional radiotracer injection...In combination with novel tracers such as FAP that may provide unique insight into the biology of primary breast tumors and drug mechanism of action, dbPET provides a cost-effective and clinically-feasibly technology that will facilitate use of PET biomarkers in clinical trials testing novel drugs in the neoadjuvant setting. Based on these preliminary results, we plan to expand our FAP-dbPET study with advanced qualitative and quantitative analyses, over time, to better measure response to therapy and ultimately to help evaluate how best to target therapy in the setting of lobular cancer."

Review • Breast Cancer • Oncology

Exploratory Analysis of [68Ga]Ga-FAP-2286 PET/CT Quantitative Parameters for Predicting Response to [177Lu]Lu-FAP-2286 Therapy in Non-small Cell Lung Cancer. (PubMed, Clin Nucl Med) - "Quantitative parameters derived from [68Ga]Ga-FAP-2286 PET/CT are valuable predictors of [177Lu]Lu-FAP-2286 treatment efficacy in NSCLC patients. Dynamic monitoring of these metrics allows for early identification of treatment responses and supports personalized therapy strategies."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FAP

Visualization of the Gallbladder on 177Lu-FAP-2286 SPECT/CT Imaging: A Potential Pitfall. (PubMed, Clin Nucl Med) - "Following radiolabeling, FAP-2286 has demonstrated favorable diagnostic performance and promising therapeutic potential in cancer. The image illustrates the accumulation of 177Lu-FAP-2286 in the gallbladder, but correlative imaging and knowledge of the radiopharmaceutical helped to avoid a diagnostic pitfall."

Journal • Oncology • Solid Tumor

Squaric-acid-engineered FAP2286: A next-generation 68Ga/177Lu theranostic ligand with synergistically enhanced affinity, hydrophilicity, and tumor retention. (PubMed, Bioorg Chem) - "Squaric acid derivatization synergistically elevates affinity, hydrophilicity, and intratumoral residence while preserving safety, establishing 68Ga/177Lu-FAP2286-SA as a clinically translatable, next-generation theranostic pair for FAP-positive malignancies."

Journal • Hematological Disorders • Oncology • FAP

Revisiting the Segmentation Threshold for Lu-177 SPECT (EANM 2025) - "1) Sphere-to-background ratios (SBRs): no background, 10:1, 5:1, 3.5:1 and 2:1 Phantom SPECT acquisitions Digital Jaszczak phantom 120 realistic noisy projections from SIMIND Monte Carlo simulation Physical Jaszczak phantom Dual-head NaI(Tl) SPECT system (Symbia T16, Siemens Healthineers, Germany) 120 projections, 25 s per view Fixed radius-of-rotation (ROR) of 24 cm 99m Tc imaging Primary energy window centered at 140 keV with a 15% window width (129.3-150.3 keV) A scatter window at 108.4-129.3 keV for the dual energy window scatter correction (SC) Low-energy high-resolution parallel hole collimators 177 Lu imaging Primary energy window centered at 208 keV with a 15% window width (192.4-223.6 keV) Two scatter windows at 161.2-192.4 keV and 223.6-244.4 keV for the triple energy window SC Medium energy general purpose parallel hole collimators Image reconstruction Filtered back projection (FBP) with Butterworth filter (cutoff frequency: 0.4, order 8 for 99m Tc; cutoff..."

A preliminary study on the safety and efficacy of 177Lu-FAP-2286 in gastrointestinal tumours with positive FAP expression. (PubMed, Radiother Oncol) - "177Lu-FAP-2286 demonstrated good feasibility and safety in treating FAP-positive gastrointestinal tumors, resulting in disease stabilization in a subset of patients."

Journal • Gastrointestinal Cancer • Oncology • Solid Tumor • FAP

Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment. (PubMed, Int J Mol Sci) - "Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., 18F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and 177Lu-FAP-2286 integrating imaging and radiotherapy). By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

An exploratory study of 177Lu-FAP-2286 combined with 177Lu-TBM-001 in the treatment of solid tumors with bone metastasis (ChiCTR) - P=N/A | N=30 | Recruiting | Sponsor: The affiliated hospital of southwest medical university; The affiliated hospital of southwest medical university

New trial • Oncology • Solid Tumor

Preclinical evaluation, and clinical translation of 68Ga/177Lu-JH04, a novel FAP-targeting radiolabeled agent (AACR 2025) - "The objective of this study is to evaluate the specificity, biodistribution, pharmacokinetics, and dosimetry of 68Ga/177Lu-JH04 through preclinical and preliminary clinical investigations, and to compare these findings with those of 68Ga/177Lu-FAP-2286. The FAP-positive cell line HT1080-FAP was employed in in vitro and in vivo studies. 68Ga/177Lu-JH04, novel FAP-targeting agent with excellent binding affinity, high tumor uptake, prolonged retention, and robust tumor-suppressive effects. These promising results encourage us to conduct further clinical research."

Preclinical • Oncology • FAP

FAUNUS: 177Lu-FAP-2286 Treatment in Urethelial Neoplasms: Utility and Safety as a Novel Treatment. (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Ankara University

New P2 trial • Oncology

177Lu-FAP-2286 Therapy in a Case of Squamous Lung Cancer. (PubMed, Clin Nucl Med) - "Radiological remission was observed on follow-up FAP imaging 7 months later with squamous cell carcinoma antigen decreased to normal level. No other abnormality monitored by routine laboratory examination was noted."

Journal • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Comprehensive Preclinical Study and Administration Protocol for 177Lu-FAP-2286: Validation, Tumor Uptake, and Dosimetry Investigations (EANM 2024) - "The validation of production and quality control processes for 177Lu-FAP-2286, along with the comprehensive preclinical studies and dosimetry investigations, demonstrate the potential for effective clinical translation. The use of lysine and arginine for kidney blockage, in combination with furosemide, shows promise in minimizing background activity in normal organs."

Preclinical • Oncology

Development of Multivalent OncoFAP Derivatives for the Tumor-Targeted Delivery of Theranostic Radionuclides (EANM 2024) - "When compared to 177Lu-FAP-2286, the most advanced FAP-targeted RLT in clinical development, 177Lu-TriOncoFAP exhibited a ~2.7-fold higher overall uptake in tumors, with a ~1.8-fold lower kidney uptake... The data presented in this work strongly supports the clinical development of 177Lu-TriOncoFAP. We are launching a Phase I clinical trial to define the 177Lu-TriOncoFAP maximum tolerated dose, evaluating its safety profile, and collecting preliminary signs of efficacy. The compound will be given as single agent or in combination with L19-IL2 in patients with multiple types of FAP-positive tumors."

Oncology • Solid Tumor • FAP • IL2