scholarly journals IN VIVO BIODISTRIBUTION OF 99mTc-MDP FOR EARLY OSTEOPOROSIS MONITORING IN OVARIECTOMIZED BALB/C MICE

2020 ◽  
Vol 21 (1) ◽  
pp. 1
Author(s):  
Ahmad Kurniawan ◽  
Yulianne Mahesa ◽  
Teguh Hafidz Ambar Wibawa ◽  
Iswahyudi Iswahyudi ◽  
Isti Daruwati ◽  
...  

Technetium-99m Methylene Diphosphonate (99mTc-MDP) has been utilized in a variety of clinical situations to identify bone areas due to the strong affinity of hydroxyapatite crystals in the mineral phase of the bone with the diphosphonate compounds. Osteoporosis is a disease characterized by decreased bone mass and increased fracture risk and represents a significant population health issue. It has been observed that 99mTc-MDP can be used for bone scintigraphy especially in case of bone cancer, but biodistribution study of 99mTc-MDP on ovariectomized mice for early monitoring of osteoporosis model remains unclear. Therefore, we aimed to investigate the biodistribution of 99mTc-MDP both in normal and ovariectomized mice. The experiment was performed on BALB/c mice weighing approximately 30 g. Mice were divided into a normal and ovariectomized group. After the first, second and third hours, mice were euthanized using the accepted protocol and the tissue of interest was collected. All tissue and blood were weighed using an analytical scale and counted for radioactivity using Automatic Gamma Counter with NaI(Tl) detector. Administration of 99mTc-MDP showed in normal mice compared with an animal model of osteoporosis, there are significant differences at 1 hour post-injection from (20.32±1.38) %ID/g decreased to (7.42±2.61) %ID/g, 2 hours from (13.75±0.01) %ID/g to (5.25±0.25) %ID/g and 3 hours from (12.18±1.44)%ID/g to (4.86±1.34) %ID/g uptake in the bones with (p<0.05). This study can be a consideration for the clinical application of 99mTc-MDP for early detection of osteoporosis conditions by looking at bone uptake and become a concern in the application for bone scintigraphy if the patient is indicated osteoporosis because it will affect visualization of the organ.

2003 ◽  
Vol 07 (07) ◽  
pp. 500-507 ◽  
Author(s):  
Bing Ma ◽  
Guolin Li ◽  
Peter Kanter ◽  
Dominick Lamonica ◽  
Zachary Grossman ◽  
...  

Pyropheophorbide-a and the corresponding 3-(1'-hexyloxyethyl)-3-devinyl derivative ( HPPH ), the tumor-avid photosensitizers were conjugated with mono- or di-bisaminoethanethiols ( N 2 S 2 ligand). The in vivo biodistribution study of the related 99m Tc complexes was performed in F-344 rats bearing Ward colon tumors at 4 h and 24 h post injection. These data show that the complexes are stable and among four tracers, HPPH di-99 m Tc N 2 S 2 conjugate reaches the highest tumor uptake (%ID/g). The larger tumors reach higher concentrations of the tracer. However, the short 6 h half life of 99 m Tc is incompatible with the 24 h imaging time, suggesting that the use of a longer-lived isotope such as 111 In could still provide a useful scanning agent, or that further structure-activity screening could yield an HPPH analog with more appropriate pharmacokinetics for tumor imaging with 99 m Tc .


2021 ◽  
Vol 22 (13) ◽  
pp. 6760
Author(s):  
Noémie Cresto ◽  
Camille Gardier ◽  
Marie-Claude Gaillard ◽  
Francesco Gubinelli ◽  
Pauline Roost ◽  
...  

Alpha-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) play crucial roles in Parkinson’s disease (PD). They may functionally interact to induce the degeneration of dopaminergic (DA) neurons via mechanisms that are not yet fully understood. We previously showed that the C-terminal portion of LRRK2 (ΔLRRK2) with the G2019S mutation (ΔLRRK2G2019S) was sufficient to induce neurodegeneration of DA neurons in vivo, suggesting that mutated LRRK2 induces neurotoxicity through mechanisms that are (i) independent of the N-terminal domains and (ii) “cell-autonomous”. Here, we explored whether ΔLRRK2G2019S could modify α-syn toxicity through these two mechanisms. We used a co-transduction approach in rats with AAV vectors encoding ΔLRRK2G2019S or its “dead” kinase form, ΔLRRK2DK, and human α-syn with the A53T mutation (AAV-α-synA53T). Behavioral and histological evaluations were performed at 6- and 15-weeks post-injection. Results showed that neither form of ΔLRRK2 alone induced the degeneration of neurons at these post-injection time points. By contrast, injection of AAV-α-synA53T alone resulted in motor signs and degeneration of DA neurons. Co-injection of AAV-α-synA53T with AAV-ΔLRRK2G2019S induced DA neuron degeneration that was significantly higher than that induced by AAV-α-synA53T alone or with AAV-ΔLRRK2DK. Thus, mutated α-syn neurotoxicity can be enhanced by the C-terminal domain of LRRK2G2019 alone, through cell-autonomous mechanisms.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.


2020 ◽  
Vol 25 ◽  
pp. 100683
Author(s):  
Georgios C. Kaiafas ◽  
Dionysia Papagiannopoulou ◽  
Αndroulla N. Miliotou ◽  
Anastasia S. Tsingotjidou ◽  
Parthenopi C. Chalkidou ◽  
...  

2019 ◽  
Vol 97 ◽  
pp. 501-512 ◽  
Author(s):  
Sara Nizzero ◽  
Feng Li ◽  
Guodong Zhang ◽  
Alessandro Venuta ◽  
Carlotta Borsoi ◽  
...  

Peptides ◽  
2009 ◽  
Vol 30 (12) ◽  
pp. 2409-2417 ◽  
Author(s):  
Alexandra Evangelou ◽  
Christos Zikos ◽  
Dimitra Benaki ◽  
Maria Pelecanou ◽  
Penelope Bouziotis ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1483
Author(s):  
Emily A. Bates ◽  
John R. Counsell ◽  
Sophie Alizert ◽  
Alexander T. Baker ◽  
Natalie Suff ◽  
...  

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.


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