Performance of 18F-FDG PET/MRI and its parameters in staging and neoadjuvant therapy response evaluation in bladder cancer.

18F-FDG PET/MRI shows potential efficacy in the diagnosis of bladder cancer (BLCA). However, the performance of 18F-FDG PET/MRI in staging and neoadjuvant therapy (NAT) response evaluation for BLCA patients remains elusive. Here, we conduct this study to evaluate the performance of 18F-FDG PET/MRI and its derived parameters for tumor staging and NAT response prediction in BLCA. Forty BLCA patients were retrospectively enrolled to evaluate the performance of 18F-FDG PET/MRI in staging and NAT response prediction in BLCA. The feasibility of using 18F-FDG PET/MRI-related parameters for tumor staging and NAT response evaluation was also analyzed. In conclusion, 18F-FDG PET/MRI is found to show good performance in the BLCA staging and NAT response prediction. Moreover, ΔSUVmean is an efficacious candidate parameter for NAT response prediction. This study highlights that 18F-FDG PET/MRI is a promising imaging approach in the clinical diagnosis and treatment for BLCA.

Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC).

PURPOSE: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC. METHODS: Five patients (all female, mean age 62 ± 8 years, ranged from 51 to 69 years) with distant metastatic DTC (dmDTC) after total thyroidectomy (TTE) and neck lymph node dissection were treated with apatinib at a dose 500 mg per day after 18F-Fluorodeoxyglucose (18F-FDG) PET/CT. The effects of apatinib on DTC were evaluated at 4 ± 1 months after treatment with apatinib. RAI therapy was then initiated. The response to apatinib and the combination therapy with RAI treatment was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1) and metabolic activity using serum thyroglobulin (Tg) and 18F-FDG PET/CT. RESULTS: Positive 18F-FDG PET/CT results were found in all patients before apatinib therapy. The immunohistochemical analysis of primary tumour tissues showed high expression of vascular endothelial growth factor receptor-2 (VEGFR-2). Four patients with follicular thyroid carcinoma (FTC) showed partial response (PR) with significant decrease in tumour size and maximum standardized uptake value (SUVmax) after 4 ± 1 month's treatment with apatinib. Further significant reduction of tumour size and SUVmax were observed in three patients after combination therapy with apatinib and RAI. Only one patient with both FTC and papillary thyroid cancer (PTC) demonstrated progressive disease (PD) after treatment with apatinib alone, however, a decrease in tumour size and SUVmax as well as serum Tg levels was achieved after the combination with RAI therapy and apatinib. CONCLUSIONS: Apatinib had significant antitumour effects on progressive distant metastatic DTC. Moreover, beneficial synergistic and complementary effects were shown when apatinib combined with RAI therapy. CLINICAL TRIAL REGISTRATION: NCT04180007, Registered November 26, 2019.

Small lesion depiction and quantification accuracy of oncological 18F-FDG PET/CT with small voxel and Bayesian penalized likelihood reconstruction.

BACKGROUND: To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification. METHODS: The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter < 2 cm) were enrolled. Six groups of PET images were reconstructed: routine voxel OSEM (RVOSEM), small voxel OSEM (SVOSEM), and SVB reconstructions with four penalty factors: 0.6, 0.8, 0.9, and 1.0 (SVB0.6, SVB0.8, SVB0.9, and SVB1.0). The routine and small voxel sizes are 4 × 4 × 4 and 2 × 2 × 2 mm3. The recovery coefficient (RC) was calculated by dividing the measured activity by the injected activity of the hot spheres in the phantom study. The SUVmax, target-to-liver ratio (TLR), contrast-to-noise ratio (CNR), the volume of the lesions, and the image noise of the liver were measured and calculated in the patient study. Visual image quality of the patient image was scored by two radiologists using a 5-point scale. RESULTS: In the phantom study, SVB0.6, SVB0.8, and SVB0.9 achieved higher RCs than SVOSEM. The RC was higher in SVOSEM than RVOSEM and SVB1.0. In the patient study, the SUVmax, TLR, and visual image quality scores of SVB0.6 to SVB0.9 were higher than those of RVOSEM, while the image noise of SVB0.8 to SVB1.0 was equivalent to or lower than that of RVOSEM. All SVB groups had higher CNRs than RVOSEM, but there was no difference between RVOSEM and SVOSEM. The lesion volumes derived from SVB0.6 to SVB0.9 were accurate, but over-estimated by RVOSEM, SVOSEM, and SVB1.0, using the CT measurement as the standard reference. CONCLUSIONS: The SVB reconstruction improved lesion contrast, TLR, CNR, and volumetric quantification accuracy for small lesions compared to RVOSEM reconstruction without image noise degradation or the need of longer emission time. A penalty factor of 0.8-0.9 was optimal for SVB reconstruction for the small tumor detection with 18F-FDG PET/CT.

68Ga-DOTA-NT-20.3 Neurotensin Receptor 1 PET Imaging as a Surrogate for Neuroendocrine Differentiation of Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-negative neuroendocrine prostate cancer (PCa) is a subtype of PCa likely to be lethal, with limited clinical diagnostic and therapeutic options. High expression of neurotensin receptor subtype 1 (NTR1) is associated with neuroendocrine differentiation of PCa, which makes NTR1 a potential target for neuroendocrine PCa. In this study, the NTR1-targeted tracer 68Ga-DOTA-NT-20.3 was synthesized, and its affinity to androgen-dependent (LNCap) and androgen-independent (PC3) xenografts was determined. Methods: 68Ga-DOTA-NT-20.3 was labeled using an automated synthesizer module, and its stability, labeling yield, and radiochemical purity were analyzed by radio-high-performance liquid chromatography. Receptor binding affinity was evaluated in NTR1-positive PC3 cells by a competitive binding assay. The biodistribution of 68Ga-DOTA-NT-20.3 in vivo was evaluated in PC3 and LNCap xenografts by small-animal PET imaging. NTR1 expression was identified by immunohistochemistry and immunofluorescence evaluation. Results: 68Ga-DOTA-NT-20.3 was synthesized successfully, with a yield of 88.07% ± 1.26%, radiochemical purity of at least 99%, and favorable stability. The NTR1 affinity (half-maximal inhibitory concentration) for 68Ga-DOTA-NT-20.3 was 7.59 ± 0.41 nM. Small-animal PET/CT of PC3 xenograft animals showed high-contrast images with intense tumor uptake, which revealed specific NTR1 expression. The tumors showed significant radioactivity (4.95 ± 0.67 percentage injected dose per gram of tissue [%ID/g]) at 1 h, which fell to 1.95 ± 0.17 %ID/g (P < 0.01, t = 8.72) after specific blockage by neurotensin. LNCap xenografts had no significant accumulation (0.81 ± 0.06 %ID/g) of 68Ga-DOTA-NT-20.3 at 1 h. In contrast, 68Ga-PSMA-11 was concentrated mainly in LNCap xenografts (8.60 ± 2.11 %ID/g), with no significant uptake in PC3 tumors (0.53 ± 0.05 %ID/g), consistent with the in vitro immunohistochemistry findings. Biodistribution evaluation showed rapid clearance from the blood and main organs (brain, heart, lung, liver, muscle, and bone), with significantly high tumor-to-liver (4.41 ± 0.73) and tumor-to-muscle (12.34 ± 1.32) ratios at 60 min after injection. Conclusion: 68Ga-DOTA-NT-20.3 can be efficiently prepared with a high yield and high radiochemical purity. Its favorable biodistribution and prominent NTR1 affinity make 68Ga-DOTA-NT-20.3 a potential radiopharmaceutical for the detection of PSMA-negative PCa and identification of neuroendocrine differentiation.