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Published on: April 25, 2025
Biodistribution of Alpha-Fetoprotein-Containing Noncovalent Complex Aimpila with Antitumor Activity
E Yu Grigor'eva1, E M Treshchalina2, A A Lipengolts2
1N. N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, Russia. grig-elen11@mail.ru.
Abstract:
Biodistribution of [125I]Aimpila (20 mg/kg) in the tumor and normal tissues, including the mammary gland tissue, after single oral dose was studied in BALB/c nude mice with T47D/ReCAF+++ human breast tumor sensitive to this drug and in closely related BALB/c nude+mice without tumors. The maximum concentration of [125I]Aimpila was in fact the same in the tumor and in the mammary gland, while the time course of its accumulation/elimination differed. The time of the maximum accumulation of the drug in the tumor was shorter and its persistence longer than in normal tissue. After 24 h, label concentration in the tumor was 4.5 times higher (p=0.002). Differences in the time course of label accumulation in the tumor were detected. The maximum ratio of tumor/blood concentrations of the preparation was recorded in 1 h after administration. [125I]Aimpila and [125I]alpha-fetoprotein accumulated in the tumor in comparable concentrations and were eliminated simultaneously at the same rate. The results of comparative analysis of accumulation of the labeled compounds in Aimpila-sensitive T47D/RECAF+++ tumor from 0.5 to 9.0 h after drug administration could be interpreted as a result of possible receptor-mediated binding of the complex with the tumor at the expense of the alpha-fetoprotein transporting part. Differences in the parameters of [125I]Aimpila biodistribution in the tumor and normal mammary tissue indirectly attested to selective antiproliferative activity of the complex.
Insights
Biodistribution of [125I]Aimpila in breast tumors showed higher concentration and longer persistence compared to normal mammary tissue. This suggests selective antiproliferative activity, with potential receptor-mediated binding via alpha-fetoprotein.
Area of Science:
- Pharmacology
- Oncology
- Radiopharmaceutical Chemistry
Background:
- Biodistribution studies are crucial for understanding drug efficacy and targeting.
- Aimpila is a drug investigated for its antiproliferative activity in breast cancer.
- T47D/ReCAF+++ is a human breast tumor model sensitive to Aimpila.
Purpose of the Study:
- To investigate the biodistribution of [125I]Aimpila in tumor and normal tissues.
- To compare the accumulation and elimination kinetics of [125I]Aimpila in tumor versus normal mammary gland.
- To explore the potential role of alpha-fetoprotein in Aimpila's tumor targeting.
Main Methods:
- BALB/c nude mice bearing T47D/ReCAF+++ human breast tumors were used.
- Single oral doses of [125I]Aimpila were administered.
- Radioactivity in tumor and normal tissues (including mammary gland) was measured over time.
- Comparative analysis with [125I]alpha-fetoprotein was performed.
Main Results:
- [125I]Aimpila showed similar maximum concentrations in tumor and mammary gland, but differed in time course.
- Tumor accumulation was faster and elimination slower, with 4.5 times higher concentration after 24h (p=0.002).
- [125I]Aimpila and [125I]alpha-fetoprotein exhibited comparable tumor accumulation and elimination kinetics.
Conclusions:
- [125I]Aimpila biodistribution parameters suggest selective antiproliferative activity against T47D/ReCAF+++ tumors.
- The results indicate potential receptor-mediated binding of Aimpila to the tumor, possibly facilitated by alpha-fetoprotein.
- Differences in biodistribution between tumor and normal tissue support Aimpila's targeted action.
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