Ex vivo activity quantification in micrometastases at the cellular scale using the α-camera technique

Area of Science:

• Nuclear medicine and oncology
• Radiopharmaceutical dosimetry
• Preclinical cancer research

Background:

• Targeted alpha-therapy (TAT) shows promise for eradicating microscopic cancer cells.
• Evaluating TAT efficacy at the cellular level is challenging due to the small scale of target lesions.
• Accurate activity quantification is essential for optimizing radiation dose delivery in TAT.

Purpose of the Study:

• To develop and validate an ex vivo method for quantifying alpha-particle activity at the cellular level.
• To assess the uptake and retention of a radiolabeled antibody in micrometastatic ovarian cancer cells.
• To determine the absorbed radiation dose delivered to individual tumor cells and micrometastases using experimental measurements.

Main Methods:

• Utilized an alpha-camera for ex vivo activity quantification in cryosectioned murine ovarian carcinoma micrometastases.
• Combined alpha-camera data with hematoxylin and eosin staining for correlating activity with tumor cell number and morphology.
• Derived time-activity curves for tumor cell clusters after injecting a (211)At-labeled radioimmunoconjugate.

Main Results:

• Demonstrated high uptake and retention of the radioimmunoconjugate on tumor cell surfaces.
• Calculated that isolated tumor cells received at least 12 Gy with 1 MBq injected activity.
• Showed that micrometastases (≤ 100 μm) received a mean absorbed dose >30 Gy due to cross-fire irradiation, despite lower per-cell uptake.

Conclusions:

• Developed a reliable ex vivo alpha-camera method for cellular-scale activity quantification.
• Characterized the behavior of a radiolabeled antibody in vivo for targeted alpha-therapy of ovarian cancer.
• This method is expected to enhance the accuracy of small-scale dosimetry and accelerate TAT optimization.