Abstract
Purpose
During [90Y]DOTATOC therapy, for determination of kidney doses a conventional approach using co-injected [111In]DOTATOC was evaluated for validity, reliability and reproducibility as well as for the influence of methodological variations and bremsstrahlung. Biologically effective doses were estimated by calculating the relative effectiveness (RE) of kidney doses.
Methods
Fractionated [90Y]DOTATOC therapy (n=20 patients, 3.1±0.7 GBq/therapy cycle, 45 therapy cycles) included co-injection of 157±37 MBq [111In]DOTATOC and a nephroprotective infusion regimen. From serial gamma camera/probe measurements, individual region of interest (ROI) sets were established and kidney doses were determined according to MIRDOSE3 (corrected for individual kidney mass) by use of three methodological variants: (1) correction for interfering organs (liver/spleen) and background activity, (2) correction for interfering organs alone and (3) no corrections. A phantom study was performed with 111 In alone and with 111In +90Y to estimate the influence of 90Y bremsstrahlung.
Results
Mean kidney dose (method 1, n=20 patients, 20 therapy cycles) was 1.51±0.60 Gy/GBq [90Y]DOTATOC (1.41±0.48 Gy/GBq for n=20 patients, 45 therapy cycles). With partial correction (method 2) or no correction (method 3) for interfering activity, kidney doses increased significantly, to 2.71±1.26 Gy/GBq and 3.15±1.22 Gy/GBq, respectively. The span of REs ranged from 1.02 to 1.24. Inter-observer variability was as high as ±32% (±2SD). 90Y bremsstrahlung accounted for a 4–11% underestimation of obtained target activity.
Conclusion
The obtained kidney doses are highly influenced by methodological variations. Full correction for interfering activity clearly underestimates kidney doses. By comparison, 90Y bremsstrahlung and variability in the relative effectiveness of kidney doses cause minor bias. Inter-observer variability must be considered when interpreting kidney doses.
Similar content being viewed by others
References
Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq90Y-DOTATOC. J Nucl Med 2002;43:610–616
Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with 90Y-DOTA0,Tyr3-octreotide and 177Lu-DOTA0, Tyr3-octreotate. J Nucl Med 2005;46 Suppl 1:83S–91S
Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med 2001;28:1552–1554
Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. 86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487)—a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003;30:510–518
Barone R, Borson-Chazot F, Valkema R, Walrand S, Chauvin F, Gogou L, et al. Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship. J Nucl Med 2005;46 Suppl 1:99S–106S
Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12:941–945
Schottelius M, Schwaiger M, Wester HJ. Rapid and high-yield solution phase synthesis of DOTA-Tyr3-octreotide and DOTA-Tyr3-octreotate using unprotected DOTA. Tetrahedron Lett 2003;44:2393–2396
Stabin MG. MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996;37:538–546
Dale RG. The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol 1985;58:515–528
Wheldon TE, O’Donoghue JA. The radiobiology of targeted radiotherapy. Int J Radiat Biol 1990;58:1–21
Cremonesi M, Ferrari M, Zoboli S, Chinol M, Stabin MG, Orsi F, et al. Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC. Eur J Nucl Med 1999;26:877–886
Krenning EP, Bakker WH, Kooij PP, Breeman WA, Oei HY, de Jong M, et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 1992;33:652–658
Foerster GJ, Engelbach MJ, Brockmann JJ, Reber HJ, Buchholz HG, Macke HR, et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of 86Y-DOTATOC and 111In-DTPA-octreotide. Eur J Nucl Med 2001;28:1743–1750
Helisch A, Foerster GJ, Reber H, Buchholz HG, Arnold R, Goke B, et al. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1386–1392
Buijs WC, Siegel JA, Boerman OC, Corstens FH. Absolute organ activity estimated by five different methods of background correction. J Nucl Med 1998;39:2167–2172
Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–122
Thames HD, Ang KK, Stewart FA, van der Schueren E. Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction? Int J Radiat Biol 1988;54:13–19
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stahl, A., Schachoff, S., Beer, A. et al. [111In]DOTATOC as a dosimetric substitute for kidney dosimetry during [90Y]DOTATOC therapy: results and evaluation of a combined gamma camera/probe approach. Eur J Nucl Med Mol Imaging 33, 1328–1336 (2006). https://doi.org/10.1007/s00259-006-0078-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-006-0078-6