A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer.

PURPOSE: This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177Lu-PSMA-EB-01 (denoted as [177Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 13 patients with mCRPC were recruited in this study. A standard 3 + 3 dose escalation protocol was performed. The following dose levels were ultimately evaluated: 1.11, 1.85, and 2.59 GBq/cycle. Patients received [177Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval. RESULTS: Patients received fractionated doses of [177Lu]Lu-LNC1003 ranging from 1.11 to 2.59 GBq per cycle. Myelosuppression was dose-limiting at 2.59 GBq, and 1.85 GBq was determined to be the MTD. The total-body effective dose for 177Lu-LNC1003 was 0.35 ± 0.05 mSv/MBq. The salivary glands were found to receive the highest estimated radiation dose, which was calculated to be 3.61 ± 2.83 mSv/MBq. The effective doses of kidneys and red bone marrow were 1.88 ± 0.35 and 0.22 ± 0.04 mSv/MBq, respectively. The tumor mean absorbed doses for bone and lymph node metastases were 8.52 and 9.51 mSv/MBq. Following the first treatment cycle, PSA decline was observed in 1 (33.3%), 4 (66.7%), and 2 (50.0%) patients at dose levels 1 (1.11 GBq), 2 (1.85 GBq), and 3 (2.59 GBq), respectively. Compared with the baseline serum PSA value, 1 (33.3%) at dose level 1 and 4 (66.6%) patients at dose level 2, presented a PSA decline after the second treatment cycle. CONCLUSION: This phase 1 trial revealed that the MTD of [177Lu]Lu-LNC1003 is 1.85 GBq. The treatment with multiple cycles at the dose of 1.11 GBq /cycle and 1.85 GBq /cycle was well tolerated. [177Lu]Lu-LNC1003 has higher tumor effective doses in bone and lymph nodes metastases while the absorbed dose in the red bone marrow should be closely monitored in future treatment studies with higher doses and multiple cycles. The frequency of administration also needs to be further explored to assess the efficacy and side effects of [177Lu]Lu-LNC1003 treatment. TRIAL REGISTRATION: 177Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic. CLINICALTRIALS: gov/ct2/show/NCT05613738.

Prospective Comparison of 68Ga-FAPI versus 18F-FDG PET/CT for Tumor Staging in Biliary Tract Cancers.

Background Gallium 68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI), an imaging agent for detecting tumors, represents a promising alternative to fluorine 18 fluorodeoxyglucose (18F-FDG). Purpose To compare the potential efficacy of 68Ga-FAPI PET/CT with that of 18F-FDG PET/CT for detecting primary tumor and nodal and distant metastases in biliary tract cancer (BTC) and to explore the impact (tumor staging) of 68Ga-FAPI compared with 18F-FDG on clinical management of BTC. Materials and Methods This single-center prospective clinical study was performed at the Affiliated Hospital of Southwest Medical University between June 2020 and June 2021. Participants with BTC underwent both 68Ga-FAPI and 18F-FDG PET/CT. Histopathologic examination, morphologic imaging, and/or follow-up imaging served as the reference standard. The maximum standardized uptake value (SUVmax) of the primary tumor and nodal and distant metastases between 18F-FDG and 68Ga-FAPI PET/CT were compared using the paired-sample t test. Results Eighteen participants with primary or recurrent BTC were evaluated (mean age, 61 years ± 10 [SD]). The sensitivity of 68Ga-FAPI PET/CT was higher than that of 18F-FDG PET/CT for detecting primary tumors (16 of 16 [100%] vs 13 of 16 [81%]), nodal metastases (41 of 42 [98%] vs 35 of 42 [83%]), and distant metastases (99 of 99 [100%] vs 78 of 99 [79%]). 68Ga-FAPI PET/CT resulted in new oncologic findings in 10 of 18 participants and upgraded tumor staging or restaging in five of 18 participants compared with 18F-FDG PET/CT. 68Ga-FAPI PET/CT demonstrated higher sensitivity than 18F-FDG PET/CT in inflammatory processes secondary to tumor-related obstruction (seven of eight [88%] vs one of eight [13%]). 68Ga-FAPI showed lower average SUVmax in inflammatory processes than in oncologic lesions (4.9 ± 2.6 vs 10.0 ± 4.6, respectively; P = .003). Conclusion Gallium 68-labeled fibroblast-activation protein inhibitor PET/CT for tumor staging showed potential for more accurate staging of biliary tract cancer, thereby improving treatment decision making. Clinical trial registration no. ChiCTR2100044131 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis.

PURPOSE: Renal fibrosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolonging patient survival. Renal puncture examination is the gold standard for renal fibrosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04, which specifically images fibroblast activation protein (FAP) expression for renal fibrosis. METHODS: All patients underwent renal puncture before receiving [68Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [68Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations. The data obtained were analyzed. RESULTS: The [68Ga]Ga-FAPI-04 PET/CT examination results demonstrated that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe fibrosis was 3.92 ± 1.50, 5.98 ± 1.6, and 7.67 ± 2.23, respectively. CONCLUSION: Compared with renal puncture examination, non-invasive imaging of FAP expression through [68Ga]Ga-FAPI-04 PET/CT quickly demonstrates bilateral kidney conditions with high sensitivity. [68Ga]Ga-FAPI-04 PET/CT can facilitate the evaluation of disease progression, diagnosis, and the development of a treatment plan.

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy.

OBJECTIVE: Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy. ANIMALS AND METHODS: Given the synthetic versatility of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand as a metal chelator and high demand of sugar molecules such as deoxyglucose (DG) in cancer cells, we carried out the radiosynthesis of a novel radiopharmaceutical agent, namely, 177Lu-DOTA-DG, and utilized it for imaging of cancer and also for the targeted radiation therapy of cancer tissues. RESULTS: In this study, we developed an efficient radiochemical synthesis of 177Lu-DOTA-DG and evaluated its pharmacological properties in vitro/in vivo. Our results showed DOTA-DG can be labeled with 177Lu with excellent radiochemical yield at 90oC in 30min. The resulting 177Lu-DOTA-DG exhibited high degree of stability without significant radiolysis up to 120h in human serum and phosphate buffer. Favorable pharmacokinetics profile was demonstrated by rapid blood clearance in 4T1 murine tumor mice and heterogeneous whole body biodistribution of 177Lu-DOTA-DG. Further, Comet assay experiments indicated that cancer cells treated with 177Lu-DOTA-DG showed significant higher degree of DNA damage compared to cells treated with 177Lu3+ or non-treated cells. CONCLUSION: This study showed that there is a great potential of using 177Lu-DOTA-DG as an imaging and therapeutic agent for cancer diagnosis and treatment. Furthermore, this study provides valuable information for developing novel 177Lu-labeled radiopharmaceuticals.

68 Ga-DOTA-IBA Uptake in Breast cancer.

ABSTRACT: A 77-year-old woman with recently diagnosed breast cancer underwent 68 Ga-labeled DOTA-ibandronic acid ( 68 Ga-DOTA-IBA) PET/CT scan for the evaluation of bone metastases. The examination revealed increased tracer uptake, indicating that the cervical vertebrae presented osteoblastic metastasis. Interestingly, the breast cancer also showed enhanced activity of 68 Ga-DOTA-IBA.

Metastatic Lung Adenocarcinoma Received Combined 177 Lu-FAP-2286 Radiation Therapy and Targeted Therapy.

ABSTRACT: A 56-year-old man with metastatic lung adenocarcinoma received combined 177 Lu-FAP-2286 radiation therapy and targeted therapy. After 1 treatment cycle, improvement of symptoms and radiological remission was observed. Moreover, the patient did not report any adverse effects.

Elevated FAPI Activity in an Adult Brodie Abscess.

ABSTRACT: We report an adult Brodie abscess with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast activating protein inhibitor), mimicking bone metastasis. Our case illustrates that Brodie abscess should also be contemplated in the differential diagnosis of osteolytic lesions with increased 68 Ga-FAPI uptake.

177 Lu-FAP-2286 Therapy in a Metastatic Bone Malignant Solitary Fibrous Tumor.

ABSTRACT: A 57-year-old woman with a metastatic bone malignant solitary fibrous tumor received 177 Lu-FAP-2286 therapy. After 1 treatment cycle, 68 Ga-FAP-2286 PET/CT revealed remission of the lesions. Moreover, the patient did not report any adverse effects.

Mesenteric Mesonephric Adenocarcinoma on 68 Ga-FAPI PET/CT.

ABSTRACT: Mesenteric mesonephric adenocarcinoma is an uncommon mesenteric neoplasm, which was arising from the mesonephric remnant of the female reproductive tract. Herein, we report the 68 Ga-FAPI PET/CT findings in a 66-year-old woman with mesenteric mesonephric adenocarcinoma.

Elevated FAPI Activity in Ulcerative Fungal Esophagitis.

ABSTRACT: We report a case of ulcerative fungal esophagitis with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast-activating protein inhibitor). Our findings suggest that ulcerative fungal esophagitis should be considered in the differential diagnosis of cancer-like esophageal mass with increased 68 Ga-FAPI uptake.

Role of 68Ga-FAPI-04 PET/CT in the Initial Staging of Esophageal Cancer.

AIM: To investigate the clinical value of 68Ga-FAPI-04 PET/CT for initial staging of esophageal cancer. METHODS: A total of 44 newly diagnosed patients with esophageal cancer were included in the analysis on the basis of postoperative pathology or clinical and radiologic follow-up. RESULTS: All primary lesions showed increased 68Ga-FAPI-04 uptake, with an SUVmax of 14.92 ± 6.91. A total of 561 lymph nodes were verified by surgery (507) or clinical and radiologic follow-up (54), of which 92 lymph nodes were diagnosed as showing metastases. Seventy-five lymph nodes with metastases showed positive findings on 68Ga-FAPI-04, with a diameter of about 1.06 ± 0.53 cm and SUVmax of 8.10±4.71. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for lymph node metastasis detection were 81.5%, 99.3%, 96.6%, 96.2%, and 96.5%, respectively. CONCLUSION: 68Ga-FAPI-04 PET/CT showed good diagnostic performance in detecting lymph node metastases of esophageal cancer.

Comparison of 18 F-FDG and 68 Ga-FAPI-04 Uptake in Postoperative Re-evaluation of Gastric, Duodenal, and Colorectal Cancers.

PURPOSE: To compare the potential efficacy of 68 Ga-FAPI-04 PET/CT with that of 18 F-FDG PET/CT for detecting tumor recurrence and nodal and distant metastases in gastric, duodenal, and colorectal cancers. METHODS: This single-center retrospective clinical study was performed at the Affiliated Hospital of Southwest Medical University between January 2020 and June 2022. Participants with gastric, duodenal, and colorectal cancers after curative resection underwent both 68 Ga-FAPI-04 and 18 F-FDG PET/CT. Histopathologic examination, morphologic imaging, and/or follow-up imaging served as the reference standards. The SUV max of the tumor recurrence and nodal and distant metastases between 18 F-FDG and 68 Ga-FAPI-04 PET/CT were compared using the paired-sample t test. RESULTS: Forty-one participants with gastric, duodenal, and colorectal cancers were enrolled in the study (median age, 51 years; range, 19-75 years). The sensitivity of 68 Ga-FAPI-04 PET/CT was higher than that of 18 F-FDG PET/CT for detecting tumor recurrence (6 of 6 [100%] vs 4 of 6 [67%]), nodal metastases (92 of 92 [100%] vs 31 of 92 [34%]), and distant metastases (28 of 30 [93%] vs 20 of 30 [67%]). CONCLUSION: 68 Ga-FAPI-04 PET/CT for tumor re-evaluation showed potential for more accurate performance of gastric, duodenal, and colorectal cancers, thereby improving treatment decision-making.

Early Detection of Gastric Intramucosal Adenocarcinoma on 68 Ga-FAPI PET/CT.

ABSTRACT: 18 F-FDG PET/CT may sometimes not be an ideal imaging method for gastric adenocarcinoma. Because of the unstable physiological uptake of 18 F-FDG in the gastrointestinal tract and muscles, it may interfere with the detection of lesions. We present a case of gastric intramucosal adenocarcinoma detected by 68 Ga-FAPI PET/CT in a patient with nasopharyngeal carcinoma.