[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers.

BACKGROUND: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. METHODS: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. RESULTS: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. CONCLUSION: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.

Initial preclinical evaluation of 68 Ga-DOTA-(Ser) 3 -LTVSPWY peptide as a PET radiotracer for glioblastoma targeting and imaging.

PURPOSE: Imaging of glioblastoma multiform (GBM) tumor using 68 -Galium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid-Ser-Ser-Ser-Leu-Thr-Val-Ser-Pro-Trp-Tyr ( 68 Ga-DOTA-(Ser)3-LTVSPWY) as a PET radiotracer for HER2 receptor due to fact that this receptor plays a pivotal role in the tumorigenesis and tumor progression in a wide range of cancer. METHODS: 68 Ga-DOTA-(Ser) 3 -LTVSPWY was produced with high radiochemical purity. The affinity and specificity of this radiotracer toward HER2 receptor on the surface of glioma glioblastoma (U-87 MG) cell line were evaluated. Furthermore, the biodistribution and PET imaging of this radiolabeled peptide were investigated on xenografted U-87 MG tumor-bearing mice. RESULTS: The in-vitro specific binding study revealed that the 68 Ga-DOTA-(Ser) 3 -LTVSPWY binds to different cell lines with respect to their level of HER2 expression. The calculated K D and B max of radiolabeled peptide toward U-87 MG cell line were 5.5 ± 2.4 nmol/l and (2.4 ± 0.3) × 10 5 receptors per cell, respectively. The highest tumor uptake was observed at 30-min postinjection, whereas the tumor-to-muscle ratio was about four-fold. The acquired PET images distinctively show tumor site, which was blocked with excess nonlabeled peptide that revealed specific in-vivo targeting of 68 Ga-DOTA-(Ser) 3 -LTVSPWY for glioma. CONCLUSION: 68 Ga-DOTA-(Ser) 3 -LTVSPWY specifically recognizes HER2 receptors and could be a potential candidate for GBM imaging.

Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients With Relapsed or Refractory Cancers: A Preliminary Study.

INTRODUCTION: Fibroblast activation protein (FAP) is a member of the serine protease family and has a high expression in the stroma of approximately 90% of epithelial malignancies. The present investigation aimed to assess the feasibility, safety, and dosimetry data of 177Lu-FAPI-46 in diverse malignancies. PATIENTS AND METHODS: Patients with advanced cancers with nonoperable tumors, or tumors refractory to conventional therapies, were enrolled. Treatment included escalating doses of 177Lu-FAPI-46 (1.85-4.44 GBq) per cycle using a combination of clinical and statistical expertise design, and intervals of 4 to 6 weeks were considered between the cycles. Biodistribution and dosimetry were examined by whole-body scans. We applied the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 to measure peptide-targeted radionuclide therapy (PTRT)-associated toxicity. RESULTS: A total of 21 patients (11 females and 10 males) with a median age of 50 years (range, 6-79 years) were investigated. Of 21 participants, 18 cases were selected for PTRT. Overall, 36 PTRT cycles were performed. The median number of PTRT cycles and the median injected amount of activity in each cycle were 2 and 3.7 GBq, respectively. The dosimetric analysis revealed median absorbed doses of 0.026, 0.136, 0.886, and 0.02 with ranges of 0.023-0.034, 0.001-0.2, 0.076-1.39, and 0.002-0.2 mGy/MBq for the whole body, liver, kidneys, and spleen, respectively. The therapy was well tolerated in almost all patients. CONCLUSIONS: The findings of this preliminary investigation might indicate the potential feasibility and safety of PTRT using 177Lu-FAPI-46 for different aggressive tumors. Moreover, the current study could be beneficial in determining the suitable amount of activity for a phase 2 study.

Targeting and imaging of HER2 overexpression tumor with a new peptide-based 68Ga-PET radiotracer.

Human epidermal growth factor receptor 2 (HER2) overexpression, as a predictive biomarker, is associated with more tumor aggressiveness and worse clinical outcomes in cancer, whereas it's accurate identification has led to the choice of effective treatments in many patients. In this study, a peptide-based PET probe (68Ga-DOTA-(Ser)3-LTVSPWY) was developed for imaging HER2 expression in tumors. The DOTA-(Ser)3-LTVSPWY was labeled with 68Ga and then was evaluated in vitro with HER2-positive SKOV-3 cell line; moreover, the in vivo biodistribution and PET/CT imaging were performed in xenografted tumor-bearing nude mice. The 68Ga-DOTA-(Ser)3-LTVSPWY displayed the high radiochemical purity greater than 95% and good stability in normal saline and human serum. The cellular binding experiments showed that the cell uptake in HER2-positive ovarian cancer cells could be effectively blocked by non-labeled peptide. The Kd and Bmax values for radiolabeled peptide were obtained at 2.5 ± 0.6 nM and (3.4 ± 0.2) × 105 sites per cell, respectively. Biodistribution study demonstrated that tumor-to-blood and tumor-to-muscle ratios were about 1.73 ± 0.36 and 3.78 ± 0.17 at 120 min after the injection of the radiolabeled peptide, respectively. Tumor imaging by PET/CT exhibited high contrast tumor image at 60 min after injection in animal models. Consequently, the results were indicative of the specific accumulation of 68Ga-DOTA-(Ser)3-LTVSPWY peptide in HER2-positive tumors and the suitability of its application as a PET probe for the diagnosis of HER2-overexpression tumor.