177Lu-DOTATATE receptor radionuclide therapy: Internal dosimetry estimates and considerations for practical protocols

Objectives Therapy with 177Lu-DOTATATE has shown efficacy for the treatment of somatostatin receptor expressing tumors (T), with apparent low risks of nephrotoxicity. Aim of this study was to derive dosimetry estimates, assessing whether 33.3GBq of 177Lu-DOTATATE divided in 6 cycles were compatible with kidney safety. Possible correlation of T and organ uptakes vs. absorbed doses was also investigated to possibly simplify data collection for dosimetry.

Methods Dosimetry was performed in 20pts. Blood, urine, whole body images (attenuation corrected; 1,3,16,24,48,60h p.i.) were analized. Number of Disintegrations(ND) and average absorbed doses(Dav) were assessed in organs and T(OLINDA/EXM), with actual mass correction; uniform activity distribution was assumed. For renal cortex, the influence of activity distribution was also explored based on published DoseVolumeHistograms(DVH) for (i)uniform (Dav to kidneys as representative also of the cortex) and (ii)inhomogeneous activity distribution (Konijnenberg,2007). Biological Effective Doses (BEDs) (i) and Equivalent Uniform BEDs (EUBEDs) (ii) were compared.

Results Median(range) Dav(Gy/GBq): 0.6(0.5-17) kidneys; 0.2(0.1-0.3) liver; 0.6(0.3-2.9) spleen; 0.04(0.02-0.06) marrow; 0.05(0.03-0.10) total body, a wide range for T (0.6-55) Gy/GBq. Median BED (i) was 20(11-40)Gy, but in one patient(BED=65Gy); EUBED (ii) was about 15%lower. Considering both models, patients’ variation and no risk factors, results did not suggest a threat for kidneys with 33.3GBq, 6 cycles in all patients but one. %uptake vs. dose correlation coefficients r2 were: red marrow <0.4 at any time; kidneys, spleen <0.4 at<48 h, 0.7 at 60h; T >0.9 any time after 24h.

Conclusions Results support the tolerability of 33.3GBq of 177Lu-DOTATATE in 6 cycles in almost all cases. Caution is recommended, and individual dosimetry with complete data collection at the first cycle. In following cycles, acceptable estimates are feasible by a single image 1 day pi. for T only, or 3days pi. for kidneys, spleen, and T