Dose Mapping After Endoradiotherapy with 177Lu-DOTATATE/DOTATOC by a Single Measurement After 4 Days

Dosimetry of organs and tumors helps to assess risks and benefit of treatment with 177Lu-DOTATATE/DOTATOC. However, it is often not performed in clinical routine because of additional efforts, the complexity of data collection and analysis, and the additional burden for the patients. Aiming at a simplification of dosimetry, we analyzed the accuracy of a theoretically substantiated approximation, which allows the calculation of absorbed doses from a single measurement of the abdominal activity distribution. Methods: Activity kinetics were retrospectively assessed from planar images in 29 patients with neuroendocrine tumors (NETs; n = 21) or meningioma (n = 8) after the administration of 177Lu-DOTATATE (n = 22) or 177Lu-DOTATOC (n = 7). Mono- or biexponential functions were fitted to measured data in 54 kidneys, 25 livers, 27 spleens, and 30 NET lesions. It was evaluated for each fit function how well the integral over time was represented by an approximation calculated as the product of the time tl of a single measurement, the expected reading at time tl, and the factor 2/ln(2). Tissue-specific deviations of the approximation from the time integral were calculated for time points tl of 24, 48, 72, 96, 120, and 144 h. Results: The correlation between time integral and approximation improved with increasing time tl. Pearson r exceeded 0.95 for a tl of 96 h or more in all tissues. The lowest maximum errors were observed at a tl of 96 h, with deviations of the approximation from the time integral of median +5% (range, −9% to +17%) for kidneys, +6% (range, −7% to +12%) for livers, +8% (range, +2% to +20%) for spleens, and +6% (range, −11% to +16%) for NET lesions. Accuracy was reduced for measurements after 72 or 120 h. For measurements after 24, 48, and 144 h, the approximation led to large deviations for some of the patients, in particular unacceptable underestimates of the absorbed dose to the kidneys. Conclusion: A single quantitative measurement of the abdominal activity concentration by SPECT/CT 4 d after the administration of 177Lu-DOTATATE/DOTATOC provides a 3-dimensional dose map and can be used to estimate the doses actually absorbed in the treatment cycle with minor additional resources and effort.

[1]  E. Demirci,et al.  Practical Guidance on Peptide Receptor Radionuclide Therapy , 2020, Nuclear Medicine Seminars.

[2]  J. Berlin,et al.  Phase 3 Trial of 177Lu‐Dotatate for Midgut Neuroendocrine Tumors , 2017, The New England journal of medicine.

[3]  P. Bernhardt,et al.  Radiation exposure of the spleen during 177Lu-DOTATATE treatment and its correlation with haematological toxicity and spleen volume , 2016, EJNMMI Physics.

[4]  A. Buck,et al.  The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy , 2016, Oncotarget.

[5]  M. Tenhunen,et al.  Effect of calculation method on kidney dosimetry in 177Lu-octreotate treatment , 2016, Acta oncologica.

[6]  A. Celler,et al.  MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy , 2016, The Journal of Nuclear Medicine.

[7]  H. Biersack,et al.  Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[8]  Eva Forssell-Aronsson,et al.  Renal function affects absorbed dose to the kidneys and haematological toxicity during 177Lu-DOTATATE treatment , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  H. Biersack,et al.  Long-Term Hematotoxicity After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate , 2013, The Journal of Nuclear Medicine.

[10]  M. Iori,et al.  Kidney Dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors , 2013, BioMed research international.

[11]  Markus Luster,et al.  EANM Dosimetry Committee Series on Standard Operational Procedures for Pre-Therapeutic Dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[12]  M. Cremonesi,et al.  The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[13]  M. Lubberink,et al.  Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177Lu-DOTA-Octreotate Treatment , 2013, The Journal of Nuclear Medicine.

[14]  Mathias Schreckenberger,et al.  One Single-Time-Point Kidney Uptake From OctreoScan Correlates With Number of Desintegrations Measured Over 72 Hours and Calculated for the 6.7 Hours Half-Life Nuclide 177Lu , 2012, Clinical nuclear medicine.

[15]  Eric C Frey,et al.  Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy. , 2012, Medical physics.

[16]  Eva Forssell-Aronsson,et al.  Estimation of absorbed dose to the kidneys in patients after treatment with 177Lu-octreotate: comparison between methods based on planar scintigraphy , 2012, EJNMMI Research.

[17]  H. Lundqvist,et al.  Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy , 2012, Acta oncologica.

[18]  Michael S. Hofman,et al.  Quantitative 177Lu SPECT (QSPECT) imaging using a commercially available SPECT/CT system , 2011, Cancer imaging : the official publication of the International Cancer Imaging Society.

[19]  L. Strigari,et al.  Dosimetry is alive and well. , 2010, Cancer biotherapy & radiopharmaceuticals.

[20]  Michael Ljungberg,et al.  177Lu‐[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy , 2010, Cancer.

[21]  Anders Sundin,et al.  Individualized dosimetry in patients undergoing therapy with 177Lu-DOTA-D-Phe1-Tyr3-octreotate , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[22]  Stephen R. Thomas,et al.  MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry—Standardization of Nomenclature , 2009, Journal of Nuclear Medicine.

[23]  E. Krenning,et al.  Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  E. P. Krenning,et al.  Comparison of [177Lu-DOTA0,Tyr3]octreotate and [177Lu-DOTA0,Tyr3]octreotide: which peptide is preferable for PRRT? , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[25]  Michael G Stabin,et al.  OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  B. Wessels,et al.  MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.