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
64
Cu and
...225
Ac-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 (
177
Lu)-labelled FAPI-46 and alpha-emitter (
225
Ac)-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
18
FFAPI-74 (12.4 ± 1.7 MBq) for the companion imaging. The biodistribution of
177
LuFAPI-46 and
225
AcFAPI-46 were evaluated in the xenograft model (total
n
= 12). For the determination of treatment effects,
177
LuFAPI-46 and
225
AcFAPI-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
177
LuFAPI-46, and 3 kBq (
n
= 3), 10 kBq (
n
= 2), 30 kBq (
n
= 6), control (
n
= 7) for
225
AcFAPI-46. Tumour sizes and body weights were followed.
Results
18
FFAPI-74 showed rapid clearance by the kidneys and high accumulation in the tumour and intestine 1 h after administration.
177
LuFAPI-46 and
225
AcFAPI-46 also showed rapid clearance by the kidneys and relatively high accumulation in the tumour at 3 h. Both
177
LuFAPI-46 and
225
AcFAPI-46 showed tumour-suppressive effects, with a mild decrease in body weight. The treatment effects of
177
LuFAPI-46 were relatively slow but lasted longer than those of
225
AcFAPI-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.
•Accelerator-BNCT produced tumor response in 71% of head and neck patients.•BNCT showed no serious adverse events such as grade 4 or 5, except hyperamylasemia.•The results support a pivotal role of ...accelerator BNCT in cancer treatment.
Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer.
In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS).
Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%).
These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.
OBJECTIVE:Here, we assess the ability of metabolic tumor volume (MTV) as measured by F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) to evaluate neoadjuvant ...chemotherapy response for patients with locally advanced esophageal cancer (EC).
BACKGROUND:Optimal methods to evaluate treatment response for EC patients have not yet been established. Although previous studies have reported the value of standardized uptake value (SUV), the accuracy of predicting histological response or long-term survival in EC is limited.
METHODS:In all, 102 EC patients without distant metastasis who underwent F-FDG PET/CT both before and after the preoperative chemotherapy series were analyzed.
RESULTS:The median primary tumor MTV values before and after preoperative chemotherapy were 22.55 (range 0.4–183.1) and 2.75 (0–52.9), respectively, and the median MVT reduction rate was 86.5%. We found the most significant difference in survival between PET responders and nonresponders with a cut-off value of 60% MTV reduction, using a 10% stepwise cut-off analysis 2-year progression-free survival (PFS)79.2 vs 44.4%; hazard ratio (HR) 3.397; P < 0.0001). With this cut-off value, histological response (P = 0.0091), tumor location (P = 0.0102), pT (P = 0.0011), and pN (P = 0.0110) were significantly associated with PET response. Univariate analysis of PFS indicated a correlation between PFS and tumor size, cT, decrease of primary lesion by CT, SUVmax reduction rate, MTV reduction rate, pT, pN, and pM. Multivariate analysis further identified pM (HR 3.063; P = 0.0279) and MTV reduction rate (HR 2.471; P = 0.0263) to be independent prognostic predictors, but not decrease of primary lesion by CT or SUVmax reduction rate.
CONCLUSION:MTV change is clinically useful in predicting both long-term survival and histological response to preoperative chemotherapy in EC patients, after determining the optimal cut-off value based on survival analysis.
Resting-state networks (RSNs) exhibit spontaneous functional connectivity in the resting state. Previous studies have evaluated RSNs mainly based on spontaneous fluctuations in blood oxygenation ...level-dependent (BOLD) signals during functional magnetic resonance imaging (fMRI). However, separation between regional increases in cerebral blood flow (CBF) and oxygen consumption is theoretically difficult using BOLD-fMRI. Such separation can be achieved using quantitative
O-gas and water positron emission tomography (PET). In addition,
F-FDG PET can be used to investigate functional connectivity based on changes in glucose metabolism, which reflects local brain activity. Previous studies have highlighted the feasibility and clinical usefulness of
F-FDG-PET for the analysis of RSNs, and recent studies have utilized simultaneous PET/fMRI for such analyses. While PET provides seed information regarding the focus of the abnormalities (e.g., hypometabolism and reduced target binding), fMRI is used for the analysis of functional connectivity. Thus, as PET and fMRI provide different types of information, integrating these modalities may aid in elucidating the pathological mechanisms underlying certain diseases, and in characterizing individual patients.
For radiological diagnosis and radionuclide therapy, X-ray and gamma-ray imaging technologies are essential. Single-photon emission tomography (SPECT) and positron emission tomography (PET) play ...essential roles in radiological diagnosis, such as the early detection of tumors. Radionuclide therapy is also rapidly developing with the use of these modalities. Nevertheless, a limited number of radioactive tracers are imaged owing to the limitations of the imaging devices. In a previous study, we developed a hybrid Compton camera that conducts simultaneous Compton and pinhole imaging within a single system. In this study, we developed a system that simultaneously realizes three modalities: Compton, pinhole, and PET imaging in 3D space using multiple hybrid Compton cameras. We achieved the simultaneous imaging of Cs-137 (Compton mode targeting 662 keV), Na-22 (PET mode targeting 511 keV), and Am-241 (pinhole mode targeting 60 keV) within the same field of view. In addition, the imaging of Ga-67 and In-111, which are used in various diagnostic scenarios, was conducted. We also verified that the 3D distribution of the At-211 tracer inside a mouse could be imaged using the pinhole mode.
The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, ...using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.
BACKGROUNDSomatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are ...more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction.
METHODSMyocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7). Control pigs underwent sham operation (n = 8).
RESULTSCell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM, +7.3% ± 2.2% and SM, +5.8% ± 5.4% vs control, −4.4% ± 3.8%; P < 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM, +4.6% ± 2.2% vs control, −3.8% ± 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM, −27.6 ± 32.3 Pa and SM, −12.8 ± 27 Pa vs control, +40.5 ± 33.9 Pa; P < 0.05).
CONCLUSIONSThe iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.
Astatine-211 (
At)-labeled phenylalanine is expected to be a promising agent for targeted alpha-particle therapy for the treatment of patients with glioma. The existing reactions to prepare the ...labeled compound usually require organic solvents and metals that are toxic and hazardous to the environment. In this study, we developed a novel method wherein astatination was realized via the substitution of
At for a dihydroxyboryl group coupled to phenylalanine.
At4-astato-L-phenylalanine was obtained as the carrier-free product in aqueous medium in high radiochemical yields (98.1 ± 1.9%, n = 5). The crude reaction mixture was purified by solid-phase extraction, and the radiochemical purity of the product was 99.3 ± 0.7% (n = 5). The high yield and purity were attributed to the formation of
AtAtI and AtI
as the reactive intermediates in the astatination reaction. The reaction did not require any organic solvents or toxic reagents, suggesting that this method is suitable for clinical applications.
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