Dose Mapping After Endoradiotherapy with ¹⁷⁷Lu-DOTATATE/DOTATOC by a Single Measurement After 4 Days

Abstract

Dosimetry of organs and tumors helps to assess risks and benefit of treatment with Lu-DOTATATE/DOTATOC. However, it is often not performed in clinical routine because of additional efforts, the complexity of data collection and analysis, and the additional burden for the patients. Aiming at a simplification of dosimetry, we analyzed the accuracy of a theoretically substantiated approximation, which allows the calculation of absorbed doses from a single measurement of the abdominal activity distribution. Activity kinetics were retrospectively assessed from planar images in 29 patients with neuroendocrine tumors (NETs; = 21) or meningioma ( = 8) after the administration of Lu-DOTATATE ( = 22) or Lu-DOTATOC ( = 7). Mono- or biexponential functions were fitted to measured data in 54 kidneys, 25 livers, 27 spleens, and 30 NET lesions. It was evaluated for each fit function how well the integral over time was represented by an approximation calculated as the product of the time t of a single measurement, the expected reading at time t, and the factor 2/ln(2). Tissue-specific deviations of the approximation from the time integral were calculated for time points t of 24, 48, 72, 96, 120, and 144 h. The correlation between time integral and approximation improved with increasing time t Pearson r exceeded 0.95 for a t of 96 h or more in all tissues. The lowest maximum errors were observed at a t of 96 h, with deviations of the approximation from the time integral of median +5% (range, -9% to +17%) for kidneys, +6% (range, -7% to +12%) for livers, +8% (range, +2% to +20%) for spleens, and +6% (range, -11% to +16%) for NET lesions. Accuracy was reduced for measurements after 72 or 120 h. For measurements after 24, 48, and 144 h, the approximation led to large deviations for some of the patients, in particular unacceptable underestimates of the absorbed dose to the kidneys. A single quantitative measurement of the abdominal activity concentration by SPECT/CT 4 d after the administration ofLu-DOTATATE/DOTATOC provides a 3-dimensional dose map and can be used to estimate the doses actually absorbed in the treatment cycle with minor additional resources and effort.

Side Effects of CXC-Chemokine Receptor 4–Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation

“…Activity kinetics in the kidneys was generally biexponential, with a negative short-lived component indicating further accumulation early after the activity administration, and a dominant long-lived component. The effective half-life of the dominant component was 37 6 12 h with 1 outlier at 97 h, which is slightly shorter than typically observed in octreotide endoradiotherapy (19)(20)(21). The renal absorbed dose per unit administered activity was 1.6 6 0.7 Gy/GBq 177 Lu-pentixather without nephroprotection, which is slightly higher than in octreotide endoradiotherapy (22).…”

Technical Note: Simplified and practical pretherapy tumor dosimetry — A feasibility study for 131I‐MIBG therapy of neuroblastoma using 124I‐MIBG PET/CT

“…Madsen et al . and Hänscheid et al . both showed that single time point data can be used for estimating doses in lesions with population average data or late time point data sampling for 90 Y‐DOTATOC therapy and 177 Lu‐DOTATATE/DOTATOC therapy, respectively.…”

“…The simplest form of uptake value could be SUV; however, an SUV measured at a fixed time point may not be a good representative of time‐integrated activity in tumors because the normalization factor used for SUV calculation such as patient weight is hardly correlative with individual tumor's metabolism that governs the radiopharmaceutical uptake and absorbed dose. Although there is a single time point‐based technique called dose mapping, that method used a later time point (e.g., single measurement after 4 days for 177 Lu‐DOTATATE/DOTATOC) . For pretherapy dosimetry, which is performed within a small window of time before full therapeutic dose administration, a later time point requirement may be less desirable.…”

The Relevance of Dosimetry in Precision Medicine

“…When using a priori information from a physiologically based pharmacokinetic model combined with Bayesian information about physiologically based pharmacokinetic model parameter distribution, the administered activity could be determined with acceptable accuracy using only 2 time points (4 h and 2 d) and thus allow a considerable reduction of needed data for individual dosimetry. Hänscheid et al (41) suggested that a single quantitative 3-dimensional image might be sufficient to provide values for absorbed doses for PRRT with an accuracy of 10%-15%. However, the results of both studies need to be confirmed in larger patient cohorts.…”