Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy

Area of Science:

• Nuclear medicine
• Radiopharmaceutical therapy
• Pharmacokinetics

Background:

• Accurate dosimetry is essential for effective radionuclide therapy.
• Pre-therapeutic biodistribution is often assumed to be equivalent to therapeutic biodistribution.
• Variations in peptide agents and doses between pre-therapy and therapy are common in sst2-receptor targeting peptide therapy.

Purpose of the Study:

• To evaluate the assumption of equivalent biodistribution between pre-therapeutic measurements and therapeutic administration in sst2-receptor targeting peptide therapy.
• To determine if using different peptides or amounts for pre-therapy imaging and therapy impacts dosimetry accuracy.

Main Methods:

• Development of physiologically based pharmacokinetic models.
• Utilized gamma camera and serum measurements from ten patients with metastasizing neuroendocrine tumors using (111)In-DTPAOC.
• Compared predicted versus measured (90)Y-DOTATATE excretions and calculated residence times for pre-therapeutic and therapeutic scenarios.

Main Results:

• Predicted and measured therapeutic excretions varied by 7-31% in three patients.
• Measured pre-therapeutic and therapeutic excretions differed significantly (52-56%).
• Simulated therapeutic residence times for kidney and tumor were 3.1-fold and 2.5-fold higher, respectively, than pre-therapeutic measurements.

Conclusions:

• The assumption of equivalent biodistribution between pre-therapy and therapy is not always justified in sst2-receptor targeting peptide therapy.
• Using the same substance and amount for both pre-therapeutic measurements and therapy is recommended to minimize dosimetry inaccuracies.
• Optimizing dosimetry requires careful consideration of peptide agent and dosage consistency.