First preclinical SPECT/CT imaging and biodistribution of [(165)Er]ErCl(3) and [(165)Er]Er-PSMA-617.

BACKGROUND: (165)Er (t(1/2) = 10.4 h, E(x-ray) = 47.1 keV (59.4%) and 54.3 keV (14.3%)) is a promising radionuclide suitable for targeted Auger electron therapy of cancer. (165)Er can be produced at a relatively low cost, high yield, and high purity using small medical cyclotrons. As a late lanthanide, (165)Er is easy to label and can be used as a surrogate for other lanthanides or Ac in proof-of-concept studies. In this report, we explore the radiochemistry, in vitro, and in vivo behavior of [(165)Er]ErCl(3) and [(165)Er]Er-PSMA-617 to showcase the application of this radionuclide. Particularly, we report the first phantom and preclinical SPECT imaging of this radionuclide leveraging its characteristic X-ray photon emissions. RESULTS: The (165)Ho(p,n)(165)Er nuclear reaction using a 13 MeV cyclotron demonstrated production yields of up to 25 ± 5 MBq. µA(-1) h(-1) at the end of the bombardment. After the purification (4.0 ± 0.5 h) using a sequential combination of cation exchange and extraction chromatography, 4-h irradiation produced up to 1.5 GBq of [(165)Er]ErCl(3). High molar activity [(165)Er]Er-PSMA-617 was prepared (~ 200 MBq/nmol). [(165)Er]Er-PSMA-617 showed a LogD(7.4) value of -2.34 ± 0.24 meaning high hydrophilicity of the complex as expected. The stability of [(165)Er]Er-PSMA-617 in saline, human, and mouse serum was studied and showed intact tracer after 12 h in all three cases. [(165)Er]ErCl(3) and [(165)Er]Er-PSMA-617 were both taken up by LNCaP cells. PSMA-617 has IC(50) at nanomolar range for [(165)Er]Er-PSMA-617 in LNCaP cells. SPECT images with preclinical phantoms showed good uniformity, spatial resolution, and quantitative accuracy. SPECT/CT imaging in LNCaP tumor-bearing mice injected with [(165)Er]Er-PSMA-617 showed high tumor uptake and quantitative accuracy when comparing the results to ex vivo biodistribution %IA/g values. Mice injected with [(165)Er]ErCl(3) showed uptake in bone structures and excretion through both liver and kidneys. CONCLUSIONS: This study demonstrated the preclinical use of (165)Er for the first time. Using [(165)Er]ErCl(3) and [(165)Er]Er-PSMA-617 as examples, the radiochemistry, cell, and animal studies showed that (165)Er can be used as a tool for evaluating targeted radiopharmaceuticals. The X-ray emission from (165)Er can be used for quantitative SPECT imaging in mice.