Related Experiment Video
Updated: Jul 20, 2026
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Control of prostate cancer spheroid growth using 213Bi-labeled multiple targeted alpha radioimmunoconjugates
Jian Wang1, Syed M Abbas Rizvi, Michele C Madigan
1Centre for Experimental Radiation Oncology, Cancer Care Centre, St. George Hospital, New South Wales, Australia.
Background:
Micrometastasis is a major problem for prostate cancer (CaP) patients. Our study investigated the therapeutic potential of multiple targeted alpha-therapy (MTAT) in the treatment of CaP micrometastases (spheroids) using (213)Bi-labeled multiple targeted alpha-radioimmunoconjugates.
Methods:
The expression of multiple tumor-associated antigens (TAAs) on frozen sections of human fresh CaP tissues and spheroids cultured from DU 145 and LNCaP-LN3 CaP cell lines was detected by immunohistochemistry and flow cytometry. Targeting vectors were two monoclonal antibodies (MAbs), and plasminogen activator inhibitor type 2 (PAI2) that binds to cell surface urokinase plasminogen activator (uPA). These vectors were labeled with (213)Bi using standard methodology. DU 145 and LNCaP-LN3 spheroids were incubated with different activities of test and control alpha-conjugates (ACs), and spheroid growth was measured for volume change and growth delay over a 50-day period using light microscopy.
Results:
TAAs were expressed heterogeneously on frozen sections from human CaP tissues and CaP spheroids. MTAT combining three ACs (one-third dose of each) with an activity of 6.4 MBq/ml completely targeted small DU 145 and LNCaP-LN3 spheroids (diameter <100 microm) and slightly regressed the growth of medium spheroids (180-200 microm); MTAT with 2.2 or 4.8 MBq/ml activities delayed the growth of tumor spheroids.
Conclusions:
Our results suggest that the cytotoxicity of MTAT to CaP spheroids is highly dependent on antigenic expression, concentration of radioactivity and spheroid size. MTAT may be a potent therapeutic agent for micrometastases, effectively targeting small CaP cell clusters, and overcoming the heterogeneous expression of targeted antigens.
Insights
Multiple targeted alpha-therapy (MTAT) effectively targets small prostate cancer micrometastases. This therapy shows potential for treating cancer spread by overcoming heterogeneous antigen expression and spheroid size.
Area of Science:
- Oncology
- Radiotherapy
- Cancer Biology
Background:
- Micrometastasis poses a significant challenge for prostate cancer (CaP) patients.
- Investigated the therapeutic potential of multiple targeted alpha-therapy (MTAT) for CaP micrometastases.
Purpose of the Study:
- To evaluate the efficacy of (213)Bi-labeled multiple targeted alpha-radioimmunoconjugates in treating prostate cancer micrometastases (spheroids).
Main Methods:
- Detected tumor-associated antigens (TAAs) on CaP tissues and spheroids using immunohistochemistry and flow cytometry.
- Used monoclonal antibodies (MAbs) and plasminogen activator inhibitor type 2 (PAI2) as targeting vectors.
- Labeled vectors with (213)Bi and incubated spheroids with varying activities of alpha-conjugates (ACs), monitoring growth over 50 days.
Main Results:
- TAAs were heterogeneously expressed on CaP tissues and spheroids.
- MTAT with 6.4 MBq/ml activity completely targeted small spheroids (<100 µm) and regressed medium spheroids (180–200 µm).
- Lower MTAT activities (2.2 or 4.8 MBq/ml) delayed tumor spheroid growth.
Conclusions:
- MTAT efficacy depends on antigenic expression, radioactivity concentration, and spheroid size.
- MTAT shows promise as a therapeutic agent for micrometastases.
- MTAT can effectively target small CaP cell clusters and overcome heterogeneous antigen expression.
