A Theoretical Model for Predicting and Optimizing In Vitro Screening of Potential Targeted Alpha-Particle Therapy Drugs

2019 ◽  
Vol 191 (5) ◽  
pp. 475 ◽  
Author(s):  
Wenzong Ma ◽  
Xudong Wang ◽  
Weihao Liu ◽  
Huan Ma ◽  
Yue Su ◽  
...  
Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1088
Author(s):  
Yun Qin ◽  
Stefan Imobersteg ◽  
Alain Blanc ◽  
Stephan Frank ◽  
Roger Schibli ◽  
...  

The overexpression of cholecystokinin B receptor (CCKBR) in human cancers led to the development of radiolabeled minigastrin analogues for targeted radionuclide therapy, which aims to deliver cytotoxic radiation specifically to cancer cells. Alpha emitters (e.g., actinium-225) possess high potency in cancer cell-killing and hold promise for the treatment of malignant tumors. In these preclinical studies, we developed and evaluated CCKBR-targeted alpha particle therapy. The cellular uptake and cytotoxic effect of actinium-225 labeled and HPLC-purified minigastrin analogue [225Ac]Ac-PP-F11N were characterized in the human squamous cancer A431 cells transfected with CCKBR. Nude mice bearing A431/CCKBR tumors were used for biodistribution and therapy studies followed by histological analysis and SPECT/CT imaging. In vitro, [225Ac]Ac-PP-F11N showed CCKBR-specific and efficient internalization rate and potent cytotoxicity. The biodistribution studies of [225Ac]Ac-PP-F11N revealed CCKBR-specific uptake in tumors, whereas the therapeutic studies demonstrated dose-dependent inhibition of tumor growth and extended mean survival time, without apparent toxicity. The histological analysis of kidney and stomach indicated no severe adverse effects after [225Ac]Ac-PP-F11N administration. The post-therapy SPECT-CT images with [111In]In-PP-F11N confirmed no CCKBR-positive tumor left in the mice with complete remission. In conclusion, our study demonstrates therapeutic efficacy of [225Ac]Ac-PP-F11N without acute radiotoxicity in CCKBR-positive cancer model.


HortScience ◽  
1998 ◽  
Vol 33 (3) ◽  
pp. 506b-506
Author(s):  
Carol D. Robacker ◽  
S.K. Braman

Azalea lace bug (Stephanitis pyrioides) is the most serious pest on azalea. Results of laboratory bioassays and field evaluations of 17 deciduous azalea taxa have identified three resistant taxa: R. canescens, R. periclymenoides, and R. prunifolium. Highly susceptible taxa are `Buttercup', `My Mary', R. oblongifolium, and the evergreen cultivar `Delaware Valley White'. To determine whether in vitro techniques would have potential value in screening or selecting for resistance, or for the identification of morphological or chemical factors related to resistance, an in-vitro screening assay was developed. In-vitro shoot proliferation was obtained using the medium and procedures of Economou and Read (1984). Shoots used in the bioassays were grown in culture tubes. Two assays were developed: one for nymphs and one for adult lace bugs. To assay for resistance to nymphs, `Delaware Valley White' leaves containing lace bug eggs were disinfested with 70% alcohol and 20% commercial bleach, and incubated in sterile petri plates with moistened filter paper until the nymphs hatched. Five nymphs were placed in each culture tube, and cultures were incubated for about 2 weeks, or until adults were observed. To assay for resistance to adults, five female lace bugs were placed in each culture tube and allowed to feed for 5 days. Data collected on survival and leaf damage was generally supportive of laboratory bioassays and field results. Adult lace bugs had a low rate of survival on resistant taxa. Survival of nymphs was somewhat reduced on resistant taxa.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Dalal ◽  
Abdul Wahab Allaf ◽  
Hind El-Zein

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.


2003 ◽  
Vol 47 (8) ◽  
pp. 2685-2687 ◽  
Author(s):  
Luiz E. Bermudez ◽  
Robert Reynolds ◽  
Peter Kolonoski ◽  
Pricilla Aralar ◽  
Clark B. Inderlied ◽  
...  

ABSTRACT In vitro screening of thiacetazone derivatives indicated that two derivatives, SRI-286 and SRI-224, inhibited a panel of 25 Mycobacterium avium complex (MAC) isolates at concentrations of 2 μg/ml or lower. In mice, SRI-224 and thiacetazone had no significant activity against the MAC in livers and spleens, but treatment with SRI-286 resulted in significant reduction of bacterial loads in livers and spleens. A combination of SRI-286 and moxifloxacin was significantly more active than single drug regimens in liver and spleen.


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