In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours — impact of peptide mass
Received 2 October 2009; received in revised form 28 October 2009; accepted 25 November 2009. published online 15 January 2010.
Abstract
Objectives
The aim of this pilot study was to explore the impact of peptide mass on binding of [68Ga]-DOTATOC to neuroendocrine tumour somatostatin receptors in vivo using a tracer of variable specific radioactivity (SRA) and to show the logistic feasibility of sequential PET scans in the same patient.
Material and Methods
Nine patients with gastroenteropancreatic neuroendocrine tumours were included. Six of them underwent three sequential PET-CT examinations with intravenous injections of [68Ga]-DOTATOC proceeded by 0, 50 and 250 or 500 μg of octreotide, administered 10 min before the tracer. Three patients were examined by dynamic and static PET/CT for pharmacokinetic and dosimetric calculations. The [68Ga]-DOTATOC synthesis included preconcentration and purification of the generator eluate and microwave heating in a semi-automated in-house procedure.
Results
[68Ga]-DOTATOC synthesis and quality control were accomplished within 30 min and radiochemical purity was >95%. The tracer accumulation in the tumours varied and depended on the total amount of the administered peptide. In five of six patients, the highest tumour-to-normal tissue ratio was found when 50 μg of octreotide was preadministered. One patient showed a continuously increasing tumour uptake. Dosimetrically, a large variation in organ doses was found (kidney: 0.086–0.168 mSv/MBq; liver: 0.026–0.096 mSv/MBq; spleen: 0.046–0.226 mSv/MBq). The effective dose (0.015, 0.0067 and 0.0042 mSv/MBq) was correlated to the total amount of decays.
Discussion
Three sequential PET-CT examinations using 68Ga-based tracer was carried out in 1 day. The use of high SRA [68Ga]-DOTATOC and unlabelled octreotide indicates an optimal mass leading to better image contrast. [68Ga]-DOTATOC-PET-CT employing variable SRA may be utilised for accurate quantification of tumour uptake with subsequent dosimetry for personalized therapy management.
aDepartment of Biochemistry and Organic Chemistry, BMC, Uppsala University, Box 599, SE-751 24 Uppsala, Sweden
bUppsala Applied Science Lab, GEMS PET Systems, GE Healthcare, SE-752 28 Uppsala, Sweden
cDepartment of Radiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
dDepartment of Endocrine Oncology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
eDepartment of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala, Sweden
fDepartment of Medicinal Sciences, Clinical Physiology and Nuclear Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
gDepartment of Pharmaceutical Biosciences, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden
Corresponding author. PET Centre, Department of Biochemistry and Organic Chemistry, Uppsala University, Box 967, SE-751 09 Uppsala, Sweden. Tel.: +46 18 666900; fax: +46 18 666819.
ABSTRACT