Non-Invasive Imaging Methodologies for Assessment of Radiation Damage to Bone Marrow and Kidneys from Peptide Receptor Radionuclide Therapy

Abstract

Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [¹⁷⁷Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [¹⁸F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([^99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [¹⁸F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBR_max] baseline:1.69 ± 0.29 vs. TBR_max PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [^99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s^–1 vs. FUR PRRT: 0.0051 ± 0.0028 s^–1, p < 0.01). Conclusion: [¹⁸F]FLT PET and [^99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [¹⁷⁷Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.