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

Abstract

Purpose: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2‐receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used. Methods: Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using111In‐DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured 90Y‐DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated. Results: Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones. Conclusions: To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.

Pharmacokinetic digital phantoms for accuracy assessment of image-based dosimetry in177Lu-DOTATATE peptide receptor radionuclide therapy

“…The radiochemical state and biological processes responsible for the observed spatial redistribution of activity is likely to change with time after injection. Given the limited amount of available input data and the additional model parameters that would be required, we did not include effects of receptor-mediated saturable uptake, protein degradation and formation of radioactive metabolites (Kletting et al 2012). Hence, the physiological interpretation and general applicability of the PK model should not be overstated.…”

Optimized Peptide Amount and Activity for 90Y-Labeled DOTATATE Therapy

“…In contrast to the previously developed model (9), the binding of peptide to serum proteins was explicitly modeled to adequately describe serum activity for time points greater than 24 h.…”

“…The effect of peptide amount was investigated in animal studies (4,5). In humans, a strong effect of substance amount on the therapeutic index has been observed in previous work with monoclonal antibodies (6)(7)(8) but also peptides (9,10). Sabet et al showed that saturation of tumor-binding sites requires considerably higher amounts of peptide than for those in normal tissue (10).…”

“…Sabet et al showed that saturation of tumor-binding sites requires considerably higher amounts of peptide than for those in normal tissue (10). Recently, we developed a pharmacokinetic model to demonstrate that different amounts of peptide for dosimetry and therapy could lead to considerably different absorbed doses (9). Until now, the effects of peptide amount on the tumor-to-kidney biologically effective dose (BED) ratio has not been considered in treatment planning.…”

Compartment Biokinetic Model for 90y-Dotatoc

“…90 Y is a pure β-emitter, whose physical half-life is 64 h. The energy of the released β-particles is up to 2.28 MeV, range of beta particles in soft tissues is short, consequently killing the cells near the point of emission. However, in this type of procedure, a significant amount of 90 Y decays in other organs, causing unwanted irradiation of healthy tissue [4,5].…”