| Title |
Evaluation of two 125I-radiolabeled acridine derivatives for Auger-electron radionuclide therapy of melanoma
|
|---|---|
| Published in |
Investigational New Drugs, April 2014
|
| DOI | 10.1007/s10637-014-0086-5 |
| Pubmed ID | |
| Authors |
Maryline Gardette, Claire Viallard, Salomé Paillas, Jean-Luc Guerquin-Kern, Janine Papon, Nicole Moins, Pierre Labarre, Nicolas Desbois, Pascal Wong-Wah-Chung, Sabine Palle, Ting-Di Wu, Jean-Pierre Pouget, Elisabeth Miot-Noirault, Jean-Michel Chezal, Francoise Degoul |
| Abstract |
We previously selected two melanin-targeting radioligands [(125)I]ICF01035 and [(125)I]ICF01040 for melanoma-targeted (125)I radionuclide therapy according to their pharmacological profile in mice bearing B16F0 tumors. Here we demonstrate in vitro that these compounds present different radiotoxicities in relation to melanin and acidic vesicle contents in B16F0, B16F0 PTU and A375 cell lines. ICF01035 is effectively observed in nuclei of achromic (A375) melanoma or in melanosomes of melanized melanoma (B16F0), while ICF01040 stays in cytoplasmic vesicles in both cells. [(125)I]ICF01035 induced a similar survival fraction (A50) in all cell lines and led to a significant decrease in S-phase cells in amelanotic cell lines. [(125)I]ICF01040 induced a higher A50 in B16 cell lines compared to [(125)I]ICF01035 ones. [(125)I]ICF01040 induced a G2/M blockade in both A375 and B16F0 PTU, associated with its presence in cytoplasmic acidic vesicles. These results suggest that the radiotoxicity of [(125)I]ICF01035 and [(125)I]ICF01040 are not exclusively reliant on DNA alterations compatible with γ rays but likely result from local dose deposition (Auger electrons) leading to toxic compound leaks from acidic vesicles. In vivo, [(125)I]ICF01035 significantly reduced the number of B16F0 lung colonies, enabling a significant increase in survival of the treated mice. Targeting melanosomes or acidic vesicles is thus an option for future melanoma therapy. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 5 | 31% |
| Researcher | 3 | 19% |
| Student > Ph. D. Student | 2 | 13% |
| Student > Postgraduate | 1 | 6% |
| Unknown | 5 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 3 | 19% |
| Chemistry | 2 | 13% |
| Chemical Engineering | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 6 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 March 2015.
All research outputs
#20,263,155
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Outputs from Investigational New Drugs
#977
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Outputs of similar age
#192,871
of 225,635 outputs
Outputs of similar age from Investigational New Drugs
#15
of 16 outputs
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