Abstract
Purpose
Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of 68Ga-DOTA-octreotate.
Methods
Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on 68Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion.
Results
There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake.
Conclusion
Our results suggest that tumour sequestration of 68Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues.
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References
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.
Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTA0Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001;28:1319–25.
Sandström M, Garske U, Granberg D, Sundin A, Lundqvist H. Individualized dosimetry in patients undergoing therapy with (177)Lu-DOTA-D-Phe (1)-Tyr (3)-octreotate. Eur J Nucl Med Mol Imaging 2010;37:212–25.
Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008;35:1847–56.
Beauregard JM, Hicks RJ. Comparison of neuroendocrine tumor lesions uptake on Ga-68-octreotate-PET/CT and post-therapy Lu-177-octreotate-SPECT/CT [abstract]. J Nucl Med 2009;50:S1657.
Prasad V, Baum RP. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. Q J Nucl Med Mol Imaging 2010;54:61–7.
Boy C, Heusner TA, Poeppel TD, Redmann-Bischofs A, Unger N, Jentzen W, et al. (68)Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUV(max). Eur J Nucl Med Mol Imaging 2011;38:1224–36.
Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Prasad V, et al. Molecular imaging with (68)Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2011;38:1659–68.
Hallynck TH, Soep HH, Thomis JA, Boelaert J, Daneels R, Dettli L. Should clearance be normalised to body surface or to lean body mass? Br J Clin Pharmacol 1981;11:523–6.
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317:1098.
Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007;48:1741–8.
Kim DW, Kim CG, Park SA, Jung SA, Yang SH. Metabolic super scan in F-FDG PET/CT imaging. J Korean Med Sci 2010;25:1256–7.
Reubi JC, Schär JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000;27:273–82.
Lewis JS, Lewis MR, Cutler PD, Srinivasan A, Schmidt MA, Schwarz SW, et al. Radiotherapy and dosimetry of 64Cu-TETA-Tyr3-octreotate in a somatostatin receptor-positive, tumor-bearing rat model. Clin Cancer Res 1999;5:3608–16.
Breeman WA, Kwekkeboom DJ, Kooij PP, Bakker WH, Hofland LJ, Visser TJ, et al. Effect of dose and specific activity on tissue distribution of indium-111-pentetreotide in rats. J Nucl Med 1995;36:623–7.
Beauregard JM, Hofman MS, Pereira JM, Eu P, Hicks RJ. Quantitative (177)Lu SPECT (QSPECT) imaging using a commercially available SPECT/CT system. Cancer Imaging 2011;11:56–66.
Wang Q, Graham K, Schauer T, Fietz T, Mohammed A, Liu X, et al. Pharmacological properties of hydrophilic and lipophilic derivatives of octreotate. Nucl Med Biol 2004;31:21–30.
Vegt E, de Jong M, Wetzels JF, Masereeuw R, Melis M, Oyen WJ, et al. Renal toxicity of radiolabeled peptides and antibody fragments: mechanisms, impact on radionuclide therapy, and strategies for prevention. J Nucl Med 2010;51:1049–58.
Förster GJ, Engelbach MJ, Brockmann JJ, Reber HJ, Buchholz HG, Mäcke HR, et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide. Eur J Nucl Med 2001;28:1743–50.
Hubble D, Kong G, Michael M, Johnson V, Ramdave S, Hicks RJ. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide. Eur J Nucl Med Mol Imaging 2010;37:1869–75.
Acknowledgments
Jean-Mathieu Beauregard was supported by a fellowship bursary award from Laval University (Quebec, Canada). Professor Hicks is the recipient of a Victorian Government Translational Research Grant through the Victorian Cancer Agency to study genomic and dosimetric factors predictive of response of NET to PRRT. We would like to thank Dr. Oliver Neels and Mr. Peter Eu for preparation of GaTate and our nuclear medicine technologist team for their tireless work.
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Beauregard, JM., Hofman, M.S., Kong, G. et al. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 39, 50–56 (2012). https://doi.org/10.1007/s00259-011-1937-3
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DOI: https://doi.org/10.1007/s00259-011-1937-3