2019 Fiscal Year Research-status Report
Potential mechanism of Gadolinium penetration via intact blood-brain barriers and the effect of Gd retention to brain cancer proliferation
| Project/Area Number |
19K17224
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| Research Institution | Gunma University |
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Principal Investigator |
K AchmadA.P. 群馬大学, 大学院医学系研究科, 助教 (70806439)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | Contrast agents (GBCA) / Transmetallation / Fe(II) / Purkinje cells / Gadolinium toxicity / Gadolinium distribution |
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| Outline of Annual Research Achievements |
We analyzed the effect of Fe(II), gadopentetate (linear) and gadobutrol (macrocyclic) on Purkinje cell. The cerebellar cells of newborn mice pinkies were cultured with GBCA and/or Fe(II) for 17 days and then stained with anti-calbindin-28K (anti-CaBP) antibody and DAPI.
Incubation with Fe(II) did not cause any changes to the Purkinje cell arborization compared the control neurons. CaBP intensity and cell number per well were also similar, indicating that incubation with Fe(II) did not cause toxicity.
Gadopentetate or gadobutrol was found to induce the dendrite arborization and increase the CaBP intensity of the cerebellar Purkinje cells. Addition of Fe(II) attenuated the toxicity effect of gadopentetate, but not gadobutrol. The cell number in all group was similar with the control group.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The original plan was to culture choroid plexus and Purkinje cells together at the same time. However we encountered few issues:
1. The culture growth is different, we could not control choroid plexus growth on each batch (high variance). Adjusting both cells in on culture is a challenge:
2. Staining choroid plexus on transwell chamber is not ideal. We have to separate the staining and the experiments for distribution
Therefore, we separated these two experiments (CP and Purkinje):
a. Experiments using only cerebellar neurons to deterimine the effect of transmetallation to GBCA toxicity --> complete, currently finalizing manuscript for publication
b. Experiments using only choroid plexus to determine how GBCA pass through CP and analyze the effect of GBCA to the choroid plexus (partial results)
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| Strategy for Future Research Activity |
1. Gd transmetallation:
We will continue the experiments about transmetallation and design an experiment to prevent this in-vivo. Other endogenous metals will be used in the experiments (Zinc, Mg) due to its possible involvement in nephrogenic systemic fibrosis. We will study on the chelate to eliminate the possibility that the chelate itself is causing neurotoxicity.
2. Gd-distribution via choroid plexus:
We are adjusting the experimental method of the distribution using different size of transwell. We will further study the exact location of Gd deposition in the choroid plexus and determine the effect of GBCA and Gd transmetallation to the choroid plexus, especially to its transporter function.
3. We are using carcinoma cell line for Gd retention study, and analyze if the same effect occurs.
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| Causes of Carryover |
The funding will be used to buy more experimental animals and materials.
Antibody and testing kit will be prioritized.
For animal study, new batch of mice for breeding (C57) will be purchased. Breeding materials will be restocked in animal room.
Due to COVID-19 situation, most conference will be in the form of online web conference. Funding in this section will be used for registration of the conference. The funding for travel will be allocated to maintain experimental equipment and more experimental study for further research.
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[Journal Article] Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer2019
Author(s)
Yamaguchi A, Achmad A, Hanaoka H, Heryanto YD, Bhattarai A, Ratianto, Khongorzul E, Shintawati R, Kartamihardja AAP, Kanai A, Sugo Y, S Ishioka N, Tetsuya H, Tsushima Y
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Journal Title
BMC Cancer
Volume: 19
Pages: 1-8
DOI
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