BackgroundPreclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease.MethodFour patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose.ResultsQualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data.Conclusion[177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.

No abstract

No abstract

[Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

Our data reveal a dual mode of action of STF-31, serving either as a NAMPT or as a GLUT inhibitor, whereby the latter seems to be apparent only at higher STF-31 concentrations. The molecular basis of such a dual function and its appearance in compounds previously designated as NAMPT-specific inhibitors requires further investigation.