Impact of Tumor Burden on Quantitative [68Ga] DOTATOC Biodistribution

Rudolf A. Werner, Heribert Hänscheid, Jeffrey P. Leal, Mehrbod S. Javadi, Takahiro Higuchi, Martin A. Lodge, Andreas K. Buck, Martin G. Pomper, Constantin Lapa, Steven P. Rowe

Research output: Contribution to journalArticle

Abstract

Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [68Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([68Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [68Ga] DOTATATE, we aimed to quantitatively investigate the biodistribution of [68Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden. Procedures: Of the 44 included patients, 36/44 (82 %) patients demonstrated suspicious radiotracer uptake on [68Ga] DOTATOC positron emission tomography (PET)/X-ray computed tomography (CT). Volumes of interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUVmean) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUVmean, maximum standardized uptake value (SUVmax), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. Results: The median SUVmean was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUVmean 6.9, SUVmax 35.5, TBM 42.6 g, and TBU 1.2 %. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUVmean increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUVmean nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3 %) vs. higher TBU (>7 %), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [68Ga] DOTATOC PET/CT. Potential implications include increased normal organ dose with [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide and decreased absolute lesion detection with [68Ga] DOTATOC in high NET burden.

Original languageEnglish
Pages (from-to)790-798
Number of pages9
JournalMolecular Imaging and Biology
Volume21
Issue number4
DOIs
Publication statusPublished - Aug 15 2019
Externally publishedYes

Keywords

  • Neuroendocrine tumor
  • Quantification
  • SSTR-PET
  • Somatostatin receptor
  • Theranostics
  • [Ga]DOTATOC

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of 'Impact of Tumor Burden on Quantitative [<sup>68</sup>Ga] DOTATOC Biodistribution'. Together they form a unique fingerprint.

  • Cite this

    Werner, R. A., Hänscheid, H., Leal, J. P., Javadi, M. S., Higuchi, T., Lodge, M. A., Buck, A. K., Pomper, M. G., Lapa, C., & Rowe, S. P. (2019). Impact of Tumor Burden on Quantitative [68Ga] DOTATOC Biodistribution. Molecular Imaging and Biology, 21(4), 790-798. https://doi.org/10.1007/s11307-018-1293-9