Feasibility of single-time-point dosimetry for radiopharmaceutical therapies

Abstract

Due to challenges in performing routine personalized dosimetry in radiopharmaceutical therapies, interest in single-time-point (STP) dosimetry, particularly utilizing only one SPECT scan, is on the rise.Meanwhile, there are questions about reliability of STP dosimetry, with limited independent validations.In the present work, we analyze two STP dosimetry methods and evaluate dose errors for a number of radiopharmaceuticals based on effective half-life distributions. Method:We first challenged the common assumption that radiopharmaceutical effective half-lives across the population are Gaussian (normal) distributed. Then, dose accuracy was estimated based on two STP dosimetry methods for a wide range of potential scan-times post-injection (p.i.), for different radiopharmaceuticals applied to neuroendocrine tumors and prostate cancer. The accuracy and limitations of using each of the STP methods were discussed.Results: Log-normal distribution was shown as more appropriate to capture effective half-life distributions. The STP framework was shown as promising for dosimetry of 177 Lu-DOTATATE, and for kidney dosimetry of different radiopharmaceuticals (errors<30%). Meanwhile, for some radiopharmaceuticals, STP accuracy is compromised (e.g. in bone marrow and tumors for 177 Lu-PSMA therapies). Optimal SPECT scanning time for 177 Lu-DOTATATE is at ~72 h p.i., while 48 h p.i. would be better for 177 Lu-PSMA compounds. Conclusion:Our results demonstrate that simplified STP dosimetry methods may compromise the accuracy of dose estimates, with some exceptions such as for 177 Lu-DOTATATE and for kidney dosimetry in different radiopharmaceuticals. Simplified personalized dosimetry in the clinic continues to be a challenging task. Based on these results, we make suggestions and recommendations for improved personalized dosimetry using simplified imaging schemes. * The data of effective half-lives were published in the format of median and range only. For Studies 3 and 9, their corresponding values of mean and SD were then calculated based on method by Hozo et al 2005 (19). For Study 4, we had access to complete listing of effective half-lives. † The 95% CI of range was estimated assuming log-normal statistics, as described in the text. ‡ T eff of each individual ROI (organ or lesion) was available (i.e. complete listing of effective half-lives for all patients). § This overall dataset (29 patients) consisted primarily of 177 Lu-DOTATATE (22 patients) but also included some 177 Lu-DOTATOC ( 7patients).

Renal and Red Marrow Dosimetry in Peptide Receptor Radionuclide Therapy: 20 Years of History and Ahead

“…PRRT dosimetry requires at least two imaging time points, as tissue activity curves exhibit a bi-exponential asymmetric bell shape. This feature renders proposed single time-point estimates inaccurate [ 48 ], which is only for a single exponential starting from t = 0, the model used to propose it [ 49 ]. One time point after the maximal uptake is needed, e.g., 24 h post-injection, and another time point somewhere around one effective half-life, i.e., 48 or 72 h post 90 Y injection and 5 to 8 days post 177 Lu injection.…”

Combining External Beam Radiation and Radionuclide Therapies: Rationale, Radiobiology, Results and Roadblocks

“…This approach is resource intensive and onerous for patients as they must attend for several scans. However, recently it has been shown that, with prior knowledge of the biokinetics of the MRT agent, it is possible to estimate the integrated activity and, therefore, dose from imaging data acquired at a single time point [55]. In a 2021 study by Hou et al [55], the optimal SPECT imaging time point was determined to be 72 and 48 h after administration of [ 177 Lu]Lu-DOTATATE and [ 177 Lu]Lu-PSMA, respectively.…”

“…However, recently it has been shown that, with prior knowledge of the biokinetics of the MRT agent, it is possible to estimate the integrated activity and, therefore, dose from imaging data acquired at a single time point [55]. In a 2021 study by Hou et al [55], the optimal SPECT imaging time point was determined to be 72 and 48 h after administration of [ 177 Lu]Lu-DOTATATE and [ 177 Lu]Lu-PSMA, respectively. In a 2018 study reported by H€ anscheid et al [56], a single time point quantitative activity measurement on SPECT/CT at 96 h post-administration of [ 177 Lu] Lu-DOTA-TATE or [ 177 Lu]Lu-DOTA-TOC could be used to estimate absorbed doses.…”

Renal and Red Marrow Dosimetry in Peptide Receptor Radionuclide Therapy: 20 Years of History and Ahead

“…PRRT dosimetry requires at least two imaging time-points, as tissue activity curves exhibit a bi-exponential asymmetric bell shape. This feature makes inaccurate proposed single time-point estimates [48], which is only for a single exponential starting from t = 0, the model used to propose it [49]. One time point after the maximal uptake is needed, e.g., 24h post injection, and another time-point somewhere around one effective half-life, i.e., 48 or 72h post 90 Y injection and 5 to 8 days post 177 Lu injection.…”