Increased 68 Ga-FAPI Uptake in Capillary Hemangiomas in an Adult Patient.

ABSTRACT: A 67-year-old woman was enrolled in our 68 Ga-FAPI PET/CT tumor clinical trial due to her lung adenocarcinoma. The PET/CT scan additionally revealed increased uptake of FAPI in the tongue. Combined with the patient's medical history and the contrast-enhanced CT of the maxillofacial region, it was suspected to be a hemangioma. Subsequently, the patient underwent surgery and was diagnosed with capillary hemangioma of the left side of her tongue.

177 Lu-FAP-2286 Therapy in a Case of Recurrent Bladder Cancer With Multiple Metastatic Lesions.

ABSTRACT: We reported a 73-year-old man who was diagnosed with the recurrence of bladder tumor received 177 Lu-FAP-2286 treatment. Encouragingly, radiological remission and alleviation of his symptom were noted. In addition, the patient did not have any adverse effects.

Influence of Cirrhosis on 68Ga-FAPI PET/CT in Intrahepatic Tumors.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) is of great diagnostic value for intrahepatic tumors. However, cirrhosis may lead to increased 68Ga-FAPI uptake in background liver, affecting the diagnostic ability of 68Ga-FAPI. Purpose To assess the effect of cirrhosis on liver parenchyma and intrahepatic tumor uptake of 68Ga-FAPI and to compare the ability of 68Ga-FAPI and fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT to depict intrahepatic tumors in patients with cirrhosis. Materials and Methods In this secondary analysis of a prospective trial, patients who underwent both 68Ga-FAPI and 18F-FDG PET/CT and those who underwent only 68Ga-FAPI PET/CT between August 2020 and May 2022 were considered for inclusion in the cirrhotic or noncirrhotic group, respectively. Patients with cirrhosis were chosen via a comprehensive assessment of imaging and clinical data, and patients without cirrhosis were randomly selected. 68Ga-FAPI and 18F-FDG PET/CT data were measured by two radiologists. Between-groups and within-group data were tested with the Mann-Whitney U test and the Wilcoxon signed-rank test, respectively. Results A total of 39 patients with cirrhosis (median age, 58 years [IQR, 50-68]; 29 male; 24 intrahepatic tumors) and 48 patients without cirrhosis (median age, 59 years [IQR, 51-67]; 30 male; 23 intrahepatic tumors) were evaluated. In patients without intrahepatic tumors, the liver 68Ga-FAPI average standardized uptake value (SUVavg) was higher in the cirrhotic group than in the noncirrhotic group (median SUVavg, 1.42 [IQR, 0.55-2.85] vs 0.45 [IQR, 0.41-0.72]; P = .002). However, no difference was observed in the diagnosis of intrahepatic tumor sensitivity (98% vs 93%, respectively). When compared with 18F-FDG, the sensitivity of 68Ga-FAPI PET/CT in the detection of intrahepatic tumors in patients with cirrhosis (41% vs 98%, respectively) and maximum standardized uptake value of tumors (median SUVmax, 2.60 [IQR, 2.14-4.49] vs 6.68 [IQR, 4.65-10.08]; P < .001) were higher. Conclusion The sensitivity of 68Ga-FAPI in the diagnosis of intrahepatic tumors was not affected by cirrhosis, and diagnostic accuracy of 68Ga-FAPI was higher than that of 18F-FDG in patients with cirrhosis. © RSNA, 2023 Supplemental material is available for this article.

Increased 68Ga-FAPI Uptake in Psammomatous Meningioma in a Patient With Gallbladder Cancer.

ABSTRACT: A 70-year-old woman with a gallbladder mass was enrolled in our clinical trial of 68Ga-FAPI PET/CT study in tumors. Increased tracer uptake was noted in the gallbladder. In addition, focal uptake was localized in a lesion beside the falx cerebri. According to the location and radiological and clinical characteristics, a diagnosis of meningioma was made.

The Superiority of 68 Ga-FAPI-04 over 18F-FDG in a Case of Gallbladder Cancer.

A 56-year-old man presented with vague upper abdominal pain for more than 4 months. His abdominal ultrasound and MRI showed thickening of the neck and base of the gallbladder and nodule formation at the base of the gallbladder. 18F-FDG PET/CT revealed intense FDG uptake in the base of the gallbladder and multiple lymph nodes. 68 Ga-FAPI-04 PET/CT not only showed intense FAPI uptake in the above mentioned FDG-avid lesions but also showed intense FAPI uptake in the neck lesion of the gallbladder and some other additional lymph nodes. Finally, histopathological examination confirmed poorly differentiated tubular adenocarcinoma of the neck and base of the gallbladder. Our case illustrated that 68 Ga-FAPI-04 PET/CT may outperform 18F-FDG PET/CT in the detection of gallbladder cancer primary and metastatic lesions.

68 Ga-DOTA-FAPI-04 PET/CT Imaging of Tracheal Mucoepidermoid Carcinoma.

ABSTRACT: A 23-year-old woman presented with a dry cough and dyspnea. Contrast-enhanced CT revealed an intratracheal space-occupying lesion with continuous homogeneous enhancement and airway stenosis. The patient then underwent 68 Ga-DOTA-FAPI-04 PET/CT, which showed increased uptake of FAPI-04 by the lesion. Postoperative pathology confirmed the lesion as tracheal mucoepidermoid carcinoma. This case reports a rare site of mucoepidermoid carcinoma and highlights the potential utility of 68 Ga-DOTA-FAPI-04 PET/CT for the diagnosis of tracheal mucoepidermoid carcinoma.

Preparation, Characterization, and Preliminary Imaging Study of [188Re]Re-Ibandronate as a Novel Theranostic Radiopharmaceutical for Bone Metastasis.

Background: Bone is a common site of metastasis from a malignant tumor. Several radiopharmaceuticals are available to relieve bone pain in patients with cancer. However, every radiopharmaceutical has its own disadvantages, and there is still a need to investigate easily accessible and high bone affinity radiopharmaceuticals. Ibandronate (IBA) and 188Re were used for radiolabeling to develop and evaluate a novel type of bone-seeking radiopharmaceutical. Methods: The preparation conditions of [188Re]Re-IBA were investigated, and thin-layer chromatography was used to analyze radiochemical purity. The stability, plasma protein binding rate, lipid-water distribution coefficient, safety and biodistribution in normal mice, and bone imaging of [188Re]Re-IBA in New Zealand rabbits were studied. In addition, the nude mice model of bone metastasis was established, and biodistribution and imaging characteristics of [188Re]Re-IBA in these nude mice were studied. Results: [188Re]Re-IBA was successfully prepared with radiochemical purity >95%. The optimum preparation conditions were as follows: IBA, 0.8-1.4 mg; ascorbic acid, 0.2-0.5 mg; stannous chloride, 0.14-0.18 mg; potassium perrhenate, 0.005 mg; and [188Re]ReO4 - activity, 18.5-296 MBq, reacted for 30 min at 95°C with pH = 2. [188Re]Re-IBA demonstrated good stability, high plasma protein binding rate, good hydrophilicity, and low toxicity. The biodistribution and bone imaging in normal animals showed rapid blood clearance, high bone uptake, low uptake in the solid organs and soft tissue, and high contrast during imaging. The biodistribution and imaging of bone metastasis in nude mice showed that [188Re]Re-IBA has higher uptake in bone metastasis lesions than normal bone. Conclusions: Our study encompassed the successful preparation of [188Re]Re-IBA, a novel bone-seeking radiopharmaceutical, and confirmed it has potential in the treatment of bone metastasis and monitoring through imaging.

Increased 68Ga-FAPI Uptake by Mediastinal Benign Teratoma on 68Ga-FAPI PET/CT.

ABSTRACT: Mediastinal teratoma is a relatively rare disease that usually contains tissue from the endoderm, mesoderm, and ectoderm. We report a finding that mediastinal benign teratoma showed intense FAPI activity on 68Ga-FAPI PET/CT, which may lead to misdiagnosis of this benign lesion. It is necessary to realize that benign teratoma is also one of the reasons for the intense FAPI uptake in mediastinal masses, so as not to be misdiagnosed as a malignant tumor.

The potential utility of [68 Ga]Ga-DOTA-FAPI-04 as a novel broad-spectrum oncological and non-oncological imaging agent-comparison with [18F]FDG.

PURPOSE: This study aimed to compare the detection performance of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the patients with various oncological and non-oncological lesions. METHODS: A total of 123 patients underwent contemporaneous [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT were included in this prospective study. The maximum standard uptake value (SUVmax) was measured to compare oncological and non-oncological lesion uptake. The sensitivity, specificity, predictive values, and accuracy of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT for detecting primary, metastatic, and non-oncological lesions were calculated and compared to evaluate the detection efficacy. RESULTS: The study subjects consisted of 123 patients (69 men and 54 women; mean age 56.11 ± 11.94 years). Among the 102 patients with either newly diagnosed (82 patients) or previously treated solid tumor (20 patients), a total of 88 solid primary malignant tumors in 84/102 patients were detected. Two patients had two primary tumors each and 1 patient had three primary tumors. Among them, 58/102 and 43/102 patients had nodal (376 lesions) and distant metastases (406 lesions), respectively. Eight patients had hematological neoplasm. No malignant oncological diseases were detected in the remaining 13 patients. A total of 145 non-oncological lesions and benign tumors in 52/123 patients were detected incidentally. [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated a significantly higher uptake and detection rate for the primary (SUVmax 10.98 ± 5.83 vs. 8.36 ± 6.43, p < 0.001; sensitivity 97.67 vs. 84.89%; and accuracy 96.59 vs. 82.95%, X2 = 0.538, p = 0.021), nodal (SUVmax 10.50 ± 5.98 vs. 8.20 ± 6.29, p = 0.011; sensitivity 97.59 vs. 84.72%; and accuracy 97.34 vs. 84.31%, X2 = 2.067, p < 0.001), and distant metastatic lesions (SUVmax 9.64 ± 6.45 vs. 6.74 ± 4.83; p < 0.001; sensitivity 98.01 vs. 65.59%; and accuracy 97.04 vs. 65.51%, X2 = 4.897, p < 0.001) of solid tumor than did [18F]FDG PET/CT. [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated a lower activity (SUVmax: 6.84 ± 4.67 vs. 13.09 ± 7.29, p < 0.001) and detection rate (sensitivity 50.65 vs. 96.75%, and accuracy 51.28 vs. 95.51%, X2 = 5.166, p < 0.001) for multiple myeloma and lymphoma compared to [18F]FDG PET/CT. [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT PET/CT demonstrated a comparative activity (SUVmax 6.40 ± 3.95 vs. 5.74 ± 15.78, p = 0.729) and detection efficacy (sensitivity 86.52 vs. 72.34%, and accuracy 84.83 vs. 72.41%, X2 = 9.460, p = 0.007) for non-oncological lesion and benign tumor detection. CONCLUSIONS: Except for myeloma and lymphoma, [68 Ga]Ga-DOTA-FAPI-04 PET/CT showed a superior detection efficacy for detecting various primary and metastatic lesions than [18F]FDG PET/CT. A comparative detection utility for non-oncological lesion was obtained with both tracers. [68 Ga]Ga-DOTA-FAPI-04 could be used as a broad-spectrum tumor and inflammatory imaging agent in the clinical especially for various solid tumors and non-oncological lesions.

Bone Marrow Metastases From Gastric Adenocarcinoma on 68Ga-FAPI-04 PET/CT.

ABSTRACT: A 37-year-old woman complained of fatigue and dizziness for 4 days. Bone marrow biopsy findings were suggestive of digestive tract-derived metastases. 18F-FDG PET/CT revealed mild FDG avidity in the stomach and bone marrow, whereas 68Ga-FAPI-04 PET/CT showed strong FAPI uptake in the FDG-avid lesions. The patient was diagnosed with bone marrow metastases from gastric cancer by a bone marrow biopsy.

FAPI PET/CT research progress in digestive system tumours.

18F-fluorodeoxyglucose positron emission tomography/computed tomography has been used in clinical practice for many years. This modality is of great value for tumour diagnosis, staging, and efficacy evaluations, but it has many limitations in the diagnosis and treatment of digestive system tumours. Fibroblast activation protein is highly expressed in gastrointestinal tumours. Various isotope-labelled fibroblast activation protein inhibitors are widely used in clinical research. These inhibitors have low background uptake in the brain, liver and oral/pharyngeal mucosa and show good contrast between the tumour and background, which makes up for the lack of fluorodeoxyglucose in the diagnosis of digestive system tumours. It better displays the primary tumours, metastases and regional lymph nodes of digestive system tumours, such as oesophageal cancer, gastric cancer and liver cancer, and also provides a new method for treating these tumours. Based on this background, this article introduces the current research status of fibroblast activation protein inhibitor positron emission tomography/computed tomography in various types of digestive system malignant tumours to provide more valuable information for diagnosing and treating digestive system tumours.

68Ga-FAPI-04 PET/CT Imaging for Fibrous Dysplasia of the Bone.

ABSTRACT: 68Ga-labeled quinoline-based fibroblast activation protein inhibitors (68Ga-FAPIs) are promising agents for tumor imaging. However, some nonneoplastic lesions can also cause increased FAPI uptake. We report a case of a patient with polyostotic fibrous dysplasia who showed widespread and intense metabolic activity on 68Ga-FAPI PET/CT. Physicians should be aware that fibrous dysplasia can also cause elevated FAPI activity.

A Novel Small Cyclic Peptide-Based 68Ga-Radiotracer for Positron Emission Tomography Imaging of PD-L1 Expression in Tumors.

In the tumor microenvironment, programmed death protein 1 and programmed death protein ligand 1 (PD-L1) signaling pathways help tumors escape the immune system. We designed a gallium-68 (68Ga)-labeled small-molecule peptide-targeting PD-L1 and used positron emission tomography/computed tomography (PET/CT) to detect and dynamically monitor the expression level of PD-L1 in tumors. S-Cyclo(ETSK)-SF-NH2 (SETSKSF) is a cyclic peptide inhibitor comprising seven amino-acid residues. We connected it with the chelating agent DOTA, labeled DOTA-SETSKSF, with the short half-life nuclide Ga-68, and measured the stability of 68Ga-2,2',2″-(10-(2-((S)-1-((3S,6S,9S,18S)-18-((S)-1-((S)-1-amino-1-oxo-3-henylpropan-2-ylamino)-3-hydroxy-1-oxopropan-2-ylcarbamoyl)-6-((R)-1-hydroxyethyl)-3-(hydroxymethyl)-2,5,8,12-tetraoxo-1,4,7,13-tetraazacyclooctadecan-9-ylamino)-3-ydroxy-1-oxopropan-2-ylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (68Ga-DOTA-SETSKSF) in normal saline (NS), phosphate-buffered saline (PBS), and fetal bovine serum (FBS) in vitro. We conducted the 68Ga-DOTA-SETSKSF affinity test, cell-specific uptake experiments, time-combined experiments, western blotting, and laser confocal experiments to confirm the expression and localization of PD-L1 at the cell level and determine the uptake. Biodistribution and imaging experiments were performed using the H1975, B16F10, and A549 tumor models. 68Ga-DOTA-SETSKSF was successfully synthesized, and the radiochemical purity was >99% after purification. The in vitro stability of 68Ga-DOTA-SETSKSF was >95% in NS, PBS, and FBS at 37 °C after 4 h of incubation. Cell-binding experiments confirmed that 68Ga-DOTA-SETSKSF exhibited high uptake in H1975 tumors with high PD-L1 expression and low uptake in A549 tumors with low PD-L1 expression. The clear half-life (T1/2) of 68Ga-DOTA-SETSKSF from the blood was 14.48 ± 3.26 min. The percentages of the injected dose per gram of tissue (%ID/g) for H1975 and A549 tumors were 5.29 ± 0.21 and 0.89 ± 0.10 at 1 h after injection, respectively. The H1975 tumor-to-muscle and tumor-to-blood ratios were 41.79 ± 5.81 and 4.75 ± 0.19 at 4 h, respectively. Apart from the H1975 tumor, the kidney and the bladder showed high accumulation because 68Ga-DOTA-SETSKSF was excreted through the urinary system. PET/CT images showed high accumulation of 68Ga-DOTA-SETSKSF in H1975 tumors and low uptake in A549 tumors, which was consistent with the results of biodistribution experiments. 68Ga-DOTA-SETSKSF is convenient to prepare, has high stability, can be used to monitor the expression of PD-L1, and has an extremely high clinical application value.

Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA.

Purpose: In this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA. Methods: The controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions. Results: The prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio. Conclusions: 68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.