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

Revisiting the segmentation threshold for Lu-177 SPECT. (PubMed, Med Phys) - "An optimal 177Lu-specific threshold (∼50%) was derived and clinically validated, differing from the conventional 42% threshold used for 99mTc. The new threshold improved segmentation accuracy across different therapeutic radiopharmaceutical distributions."

Journal • Oncology

Validation of a panel of fibroblast activation protein expressing cell line derived xenograft models as a platform for the development of targeted radioligand therapeutics (AACR 2026) - "In this study, we evaluate target expression and compare the anti-tumor efficacy of 177Lu-FAP-2286 across multiple immunocompromised mouse models bearing subcutaneous, cell line-derived tumors. Our findings underscore the critical role of model selection in preclinical development and highlight its importance for rational decision-making in RLT programs."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Dual-tracer PET/CT and cocktail therapy with [177Lu]Lu-FAP2286 and [177Lu]Lu-DOTATATE in G3 Neuroendocrine Tumors (NET). (PubMed, Eur J Nucl Med Mol Imaging) - No abstract available

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor

Fibroblast Activation Protein Inhibitor Theranostics in Sarcoma: Current Evidence and Future Directions. (PubMed, Clin Nucl Med) - "Various FAPI radiotracers, including FAPI-04, FAPI-46, and FAP-2286, offer unique pharmacokinetic properties...However, challenges remain, including FAP expression heterogeneity and the need for optimized treatment protocols. The aim of this review is to provide a comprehensive overview of the current evidence and future directions of FAPI-based theranostics in sarcoma management, highlighting its potential to improve patient outcomes."

Journal • Oncology • Sarcoma • Solid Tumor • FAP

Long-term performance evaluation of a novel 3.26 GBq 68Ge/68Ga generator. (PubMed, EJNMMI Radiopharm Chem) - "The enhancement of the 68Ge(IV) loading capacity in the 68Ge/68Ga generator, along with improved 68Ga elution efficiency, facilitates the rapid and efficient production of 68Ga. This advancement contributes to the promotion and widespread adoption of 68Ga-based radiopharmaceuticals and benefits more patients."

Journal

Comparative 18F-FDG PET/CT and FAP-targeted PET/CT Findings in Parotid Warthin Tumor. (PubMed, Clin Nucl Med) - "We report 2 cases of parotid Warthin tumors that demonstrated marked FDG uptake but absent or minimal uptake on FAP-targeted PET/CT using 68Ga-FAPI-04 and 68Ga-FAP-2286. This discordant imaging pattern suggests that FAP-targeted PET/CT may aid in distinguishing Warthin tumor from malignant lesions."

Journal • Oncology • Parotid Gland Cancer

CAAA614A12101: LuMIERE: A Phase 1/2, Multicenter, Open label, Non randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of [177Lu]Lu-FAP-2286 in Participants with an Advanced Solid Tumor (clinicaltrialsregister.eu) - P1/2 | N=36 | Recruiting | Sponsor: Novartis Pharma AG

New P1/2 trial • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer

Remarkable Response to 177Lu-PSMA and 177Lu-DOTA-IBA Cocktail Therapy in a Patient With Dual Primary Malignancies. (PubMed, Clin Nucl Med) - "A patient with metastatic atypical right lung carcinoid underwent 68Ga-FAP2286 and 68Ga-DOTATATE PET/CT scans to assess eligibility for radionuclide therapy, which revealed insufficient coverage of all lesions by either tracer. Guided by these multimodal imaging, the patient received combined 177Lu-PSMA and 177Lu-DOTA-IBA therapy. Notably, he achieved near-complete remission of both primary malignancies and all metastases after one cycle of cocktail therapy and one cycle of 177Lu-DOTA-IBA therapy."

Journal • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Head-to-head comparison of FAP-targeting single-domain antibody 4AH29 vs. peptide FAP-2286. (PubMed, EJNMMI Res) - No abstract available

Head-to-Head • Journal

177Lu-FAP-2286 Combined Chemotherapy in a Case of Thymus Nonkeratinizing Squamous Carcinoma With Superior Vena Cava Syndrome. (PubMed, Clin Nucl Med) - "68Ga-FAP-2286 PET/CT revealed significantly less intensity of the mediastinal mass comparing to pretherapy scan, as well as significant relief of SVCS. No adverse effects were observed."

Journal • Oncology • Squamous Cell Carcinoma

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