Ebrahim S Delpassand1,2, David Ranganathan2, Nilesh Wagh2, Afshin Shafie1, Ayman Gaber1, Ali Abbasi2, Andreas Kjaer3, Izabela Tworowska2, Rodolfo Núñez4. 1. Excel Diagnostics and Nuclear Oncology Center, Houston, Texas. 2. RadioMedix, Inc., Houston, Texas; and. 3. Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. 4. Excel Diagnostics and Nuclear Oncology Center, Houston, Texas rnunez@exceldiagnostics.com.
Abstract
Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic-quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted on 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic-quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were masked to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with disease or no disease, as well as those with localized versus metastatic status. Masked-reader evaluations were compared with a patient-specific standard of truth, which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intrareader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events were recorded from 64Cu-DOTATATE injection through 48 h after injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic-quality PET/CT images. After database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial standard-of-truth misread. Excellent inter- and intrareader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No adverse events were related to 64Cu-DOTATATE, and no serious adverse events were observed. Conclusion: 64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.
Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic-quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted on 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic-quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were masked to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with disease or no disease, as well as those with localized versus metastatic status. Masked-reader evaluations were compared with a patient-specific standard of truth, which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intrareader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events were recorded from 64Cu-DOTATATE injection through 48 h after injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic-quality PET/CT images. After database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial standard-of-truth misread. Excellent inter- and intrareader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No adverse events were related to 64Cu-DOTATATE, and no serious adverse events were observed. Conclusion:64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.
Authors: Alexandra I Fonseca; Vítor H Alves; Sérgio J C do Carmo; Magda Silva; Ivanna Hrynchak; Francisco Alves; Amílcar Falcão; Antero J Abrunhosa Journal: Pharmaceuticals (Basel) Date: 2022-06-07