Abstract

PurposeOver recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.MethodsIn this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.ResultsDifferences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.ConclusionThis study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.

Highlights

  • In recent years, peptide receptor radiotherapy (PRRT) using 177Lu-DOTATATE has been demonstrated to be effective for treatment of patients with metastatic neuroendocrine tumors (NETs) [1–3]. 177Lu-DOTATATE binds to somatostatin receptors present in NETs. 177Lu decays mainly in the form of β radiation, with a small part of γ radiation

  • In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to time activity concentration curve (TACC) for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT

  • This study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan

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Summary

Introduction

Peptide receptor radiotherapy (PRRT) using 177Lu-DOTATATE has been demonstrated to be effective for treatment of patients with metastatic neuroendocrine tumors (NETs) [1–3]. 177Lu-DOTATATE binds to somatostatin receptors present in NETs. 177Lu decays mainly in the form of β radiation, with a small part of γ radiation. Peptide receptor radiotherapy (PRRT) using 177Lu-DOTATATE has been demonstrated to be effective for treatment of patients with metastatic neuroendocrine tumors (NETs) [1–3]. The γ radiation (main energy 208 keV) permits post-treatment imaging that can be used to confirm that the radiopharmaceutical has reached its intended targets (primary tumor and/or metastases) and for personalized dosimetry. Personalized dosimetry calculations based on post-therapy SPECT images yield estimates of absorbed dose to tumors and normal tissues [4]. These absorbed dose estimates contribute to the planning of ongoing serial treatments, to avoid exceeding the absorbed dose threshold for vulnerable normal organs and to ensure sufficient absorbed dose to tumor, in the light of evidence of an absorbed dose-response curve, at least for pancreatic neuroendocrine tumors [5]. While it is not practical to acquire images at more than 3–4 time points, it is not possible to calculate an exact integral based on so few time points, and approximations must be made

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