Nonclinical study and applicability of the absorbed dose conversion method with a single biodistribution measurement for targeted alpha-nuclide therapy

Background We recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement, the percent injected dose/g. However, there were some mathematical ambiguities in determining the optimal timing of a single measurement of the percent injected dose/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. Methods We derived a new formalism of the RAP dose conversion method at time t. In addition, we acquired a formula to determine the optimal timing of a single measurement of the percent injected dose/g, assuming the one-compartment model for biological clearance. Results We investigated the new formalism’s performance using a representative RAP coefficient with radioactive decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, the behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG. Conclusions The RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy.

Nonclinical Study and Applicability of the Absorbed Dose Conversion Method With a Single Biodistribution Measurement for Targeted Alpha-Nuclide Therapy

BackgroundWe recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement (%ID/g). However, there were some mathematical ambiguities in determing the optimal timing of a single measurement of %ID/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. ResultsWe derived a new formalism of the RAP dose conversion method at time t and investigated the new formalism’s performance using a representative RAP coefficient with radioactive-decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, we acquired a formula to determine the optimal timing of a single measurement of %ID/g, assuming the one-compartment model for biological clearance. The behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG.ConclusionsThe RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy.

Systemic Radionuclide Palliative Therapy for Metastatic Carcinoma with Strontium 89

Metastatic carcinoma is the most common neoplasm involving the skeletal system. It is estimated that 30% to 70% of newly diagnosed cancer patients develop osseous metastases, causing intractable bone pain. A variety of treatments have been used to control bone pain associated with skeletal metastases, including analgesics, cytotoxic chemotherapy, external beam radiotherapy and systemic radio-nuclide therapy. Strontium 89 (89Sr) is a systemic radionuclide and calcium analog that has been extensively used for pain control in advanced skeletal metastatic disease. Strontium 89 offers advantages over other treatment modalities, including repeated treatments if necessary, less bone marrow suppression and toxicity and potential for cost effectiveness.