Prostate specific membrane antigen (PSMA)-ligand PET/CT is performed in patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. 18 F-PSMA-1007 is a promising PSMA-PET tracer based on clinical results, but detailed histologic confirmation has been lacking.
FBPA PET has a potential to estimate B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.
Purpose Fibroblast activation protein (FAP), which has high expression in cancer-associated fibroblasts of epithelial cancers, can be used as a theranostic target. Our previous study used 64Cu and 225Ac-labelled FAP inhibitors (FAPI-04) for a FAP-expressing pancreatic cancer xenograft imaging and therapy. However, the optimal therapeutic radionuclide for FAPI needs to be investigated further. In this study, we evaluated the therapeutic effects of beta-emitter (177Lu)-labelled FAPI-46 and alpha-emitter (225Ac)-labelled FAPI-46 in pancreatic cancer models. Methods PET scans (1 h post injection) were acquired in PANC-1 xenograft mice (n = 9) after the administration of [18F]FAPI-74 (12.4 ± 1.7 MBq) for the companion imaging. The biodistribution of [177Lu]FAPI-46 and [225Ac]FAPI-46 were evaluated in the xenograft model (total n = 12). For the determination of treatment effects, [177Lu]FAPI-46 and [225Ac]FAPI-46 were injected into PANC-1 xenograft mice at different doses: 3 MBq (n = 6), 10 MBq (n = 6), 30 MBq (n = 6), control (n = 4) for [177Lu]FAPI-46, and 3 kBq (n = 3), 10 kBq (n = 2), 30 kBq (n = 6), control (n = 7) for [225Ac]FAPI-46. Tumour sizes and body weights were followed. Results [18F]FAPI-74 showed rapid clearance by the kidneys and high accumulation in the tumour and intestine 1 h after administration. [177Lu]FAPI-46 and [225Ac]FAPI-46 also showed rapid clearance by the kidneys and relatively high accumulation in the tumour at 3 h. Both [177Lu]FAPI-46 and [225Ac]FAPI-46 showed tumour-suppressive effects, with a mild decrease in body weight. The treatment effects of [177Lu]FAPI-46 were relatively slow but lasted longer than those of [225Ac]FAPI-46. Conclusion This study suggested the possible application of FAPI radioligand therapy in FAP-expressing pancreatic cancer. Further evaluation is necessary to find the best radionuclide with shorter half-life, as well as the combination with therapies targeting tumour cells directly.
BackgroundBoron neutron capture therapy (BNCT) is a molecular radiation treatment based on the 10B (n, α) 7Li nuclear reaction in cancer cells, in which delivery of 10B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-18 F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT.MethodsRGC-6 rat glioma cells (1.9 × 107) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of 10B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES).ResultsThe highest absolute concentration of 10B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05).ConclusionsFBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.
BACKGROUND Successful bipolar radiofrequency catheter ablation (RFCA) of refractory ventricular arrhythmias (VAs) has been reported. However, the efficacy, safety, and long-term outcomes of bipolar RFCA of VAs are not fully determined.OBJECTIVE The purpose of this study was to evaluate the effectiveness and safety of bipolar RFCA in treating refractory VAs during long-term follow-up.METHODS Eighteen patients who underwent bipolar RFCA for ventricular tachycardia (VT) at 7 institutions were retrospectively investigated. Underlying heart diseases included remote myocardial infarction (n 5 3 [17%]) and nonischemic cardiomyopathy (n 5 15 [83%]). Although unipolar RFCA was performed in all patients, either it failed to suppress VT or VT recurred. The interventricular septum, left ventricular free wall, and left ventricular summit were targeted for bipolar RFCA.RESULTS Acute success (VT termination and/or noninducibility) was achieved with bipolar RFCA in 16 patients (89%). Complications during the procedure included complete atrioventricular block (n 52) and coronary artery stenosis (n 5 1). One patient underwent chemical ablation after bipolar RFCA failure. At 12-month followup, VT reoccurred in 8 patients (44%). However, in patients with recurrence, VT burden had decreased: only 4 patients underwent re-RFCA, and only 1 of the 4 required chemical ablation. In the remaining 4 patients, re-RFCA was not required, as VT was controlled by medication or an implantable cardioverter-defibrillator. CONCLUSION Bipolar RFCA is useful for acute suppression of refractory VT. Although VT recurrence rates during long-term followup were relatively high, we observed a significant reduction in VT burden.
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