ABSTRACT
Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.
ABSTRACT
Objective:To compare the effect of different β values on the semi-quantitative accuracy and image quality of 68Ga-prostate specific membrane antigen (PSMA) PET/CT imaging after partial volume effect correction (PVC). Methods:In the model experiment, image reconstruction was carried out based on block sequential regularized expectation maximization algorithm (BSREMA) with the range of β values from 100 to 1 000. Recovery coefficient (RC), contrast recovery (CR) and background variability (BV) were measured to evaluate semi-quantitative accuracy and image quality. In the clinical study, image data of 21 prostate cancer patients (age 45-78 years) who underwent 68Ga-PSMA PET/CT examination in the First Hospital of Shanxi Medical University from March 2019 to February 2020 were retrospectively collected. A total of 29 abdominal imaging positive lymph nodes were divided into the small lymph node group (diameter <10 mm; n=12) and the large lymph node group (10 mm≤diameter≤30 mm; n=17). SUV parameters including SUV max, SUV mean and peak of SUV (SUV peak) and the influence of different β values on the SUV parameters were evaluated. The signal to noise ratio (SNR) and subjective scores were used to evaluate image quality. Independent-sample t test, Kappa test and Pearson correlation analysis were used to analyze data. Results:The model experiment showed that CR, RC and BV decreased with the increase of β values. The image quality, image clarity, lesion significance, and total image scores given by nuclear medicine physicians showed strong consistency ( Kappa values: 0.65-0.87, P values: 0.026-0.043). The small lymph node group had the highest score (13 and 14) with β value of 600, while the large lymph node group had the highest score (13 and 14) with β value of 700. SNR of the two groups increased steadily within β values from 100 to 600 ( t values: 2.49-8.99, P values: 0.023-0.038). When the β value was higher than 600, SNR of the small lymph node group reached a plateau ( t values: 1.28-2.00, P values: 0.072-0.098), while the SNR of the large lymph node group continued to increase ( t values: 2.98-4.63, P values: 0.012-0.029). Before PVC, there were significant negative correlations between SUV parameters and β values ( r values: from -0.94 to -0.64, P values: 0.039-0.046). After PVC, it was found that SUV mean and SUV max still had significant negative correlation with β values ( r values: from -0.78 to -0.68, P values: 0.035-0.042), while the SUV peak showed no significant correlation with β values ( r values: -0.22, -0.28, P values: 0.069, 0.126). Conclusions:Based on subjective scores and semi-quantitative indicators, 68Ga-PSMA PET/CT is superior to select β values of 600 and 700 for image reconstruction based on BSREMA. The SUV peak of small lesions is stable after PVC and the clinical value should be explored in further.