Influence of sampling schedules on [177Lu]Lu-PSMA dosimetry

Abstract

Background: Individualized dosimetry is recommended for [ 177 Lu]Lu-PSMA radioligand therapy (RLT) which is resource-intensive and protocols are often not optimized. Therefore, a simulation study was performed focusing on the determination of efficient optimal sampling schedules (OSS) for renal and tumour dosimetry by investigating different numbers of time points (TPs). Methods: Sampling schedules with 1-4 TPs were investigated. Time-activity curves of the kidneys and two tumour lesions were generated based on a physiologically based pharmacokinetic (PBPK) model and biokinetic data of 13 patients who have undergone [ 177 Lu]Lu-PSMA I&T therapy. Systematic and stochastic noise of different ratios was considered when modelling time-activity data sets. Time-integrated activity coefficients (TIACs) were estimated by simulating the hybrid planar/SPECT method for schedules comprising at least two TPs. TIACs based on one single SPECT/ CT measurement were estimated using an approximation for reducing the number of fitted parameters. For each sampling schedule, the root-mean-squared error (RMSE) of the deviations of the simulated TIACs from the ground truths for 1000 replications was used as a measure for accuracy and precision. Results: All determined OSS included a late measurement at 192 h p.i., which was necessary for accurate and precise tumour TIACs. OSS with three TPs were identified to be 3-4, 96-100 and 192 h with an additional SPECT/CT measurement at the penultimate TP. Kidney and tumour RMSE of 6.4 to 7.7% and 6.3 to 7.8% were obtained, respectively. Shortening the total time for dosimetry to e.g. 96 h resulted in kidney and tumour RMSE of 6.8 to 8.3% and 9.1 to 11%, respectively. OSS with four TPs showed similar results as with three TPs. Planar images at 4 and 68 h and a SPECT/CT shortly after the 68 h measurement led to kidney and tumour RMSE of 8.4 to 12% and 12 to 16%, respectively. One single SPECT/CT measurement at 52 h yielded good approximations for the kidney TIACs (RMSE of 7.0%), but led to biased tumour TIACs. Conclusion: OSS allow improvements in accuracy and precision of renal and tumour dosimetry for [ 177 Lu]Lu-PSMA therapy with potentially less effort. A late TP is important regarding accurate tumour TIACs.

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

“…Limited data are available regarding simplified dosimetry of [ 177 Lu]Lu-PSMA RLT. Rinscheid et al [34] demonstrated that a single SPECT/CT measurement at 52 h p.i. yielded good approximations for the time-integrated activity coefficients of the kidney, consistent with the results of our study.…”

“…Another interesting approach for single-time-point-based renal dosimetry, originally introduced by Hänscheid et al for DOTATATE-therapies uses an approximate method to estimate the area under the timeactivity curve [33]. The principle validity of this approach also for PSMA-targeted therapies was shown by Rinscheid et al [34]. All of these studies showed that dosimetric calculations for the kidneys but also tumor lesions seem possible based on data from a single imaging time-point.…”

A Novel Time–Activity Information-Sharing Approach Using Nonlinear Mixed Models for Patient-Specific Dosimetry with Reduced Imaging Time Points: Application in SPECT/CT After 177Lu-DOTATATE

“…In addition, we chose 4h as the second time point for patient convenience as it enables imaging before discharge on the day of therapy. (13). In our analysis, the single time point mixed model often performed better than the two time point mixed model, suggesting that addition of the early measurement may not be necessary.…”

“…Exponential functions are customarily used to fit the measured time-activity data, and two or three sampling points per exponential term and measurement period up to three to five times the effective half-life are recommended (3). A number of recent studies have considered simplified personalized renal dosimetry in PRRT (4)(5)(6)(7)(8)(9)(10)(11)(12) and Lu177-PSMA therapy (13,14). In particular, methods for approximating the PRRT TIA using a single activity measurement, introduced for Lu-177 DOTATATE by Hanscheid et al (4) and for Y-90 DOTATOC by Madsen et al (5), have gained popularity.…”

Bild-basierte Patienten-individuelle Dosimetrie bei internen Radionuklidtherapien von neuroendokrinen Tumoren

“…Für die Dosimetrie in der Radionuklidtherapie ist folglich der zu erwartende Fehler für die Tumordosimetrie deutlich größer als der Fehler bei der Bestimmung der Strahlendosis auf vergleichsweise große Risikoorgane wie Leber, Nieren und Milz. Aus Sicht der Pharmakokinetik ist die Genauigkeit der Tumordosimetrie zudem stark durch den letzten verfügbaren Bildgebungszeitpunkt beeinflusst[43,54,55].Von ihrem Grundgedanken her hat die Dosimetrie im Rahmen von interner oder externer Strahlentherapie zum Ziel, die Strahlendosis des gesunden Gewebes zu minimieren, bei gleichzeitiger Maximierung der Tumordosis, um das therapeutische Fenster maximal auszuschöpfen. Für die externe Strahlentherapie ist dieser Ansatz vollständig innerhalb der klinischen Routine etabliert und umsetzbar, da im Rahmen der externen Strahlentherapie die Zieldosis auf das maligne Gewebe während der Therapiesitzung kontrolliert unter Berücksichtigung umliegender Risikoorgane eingestrahlt werden kann.…”