In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours — impact of peptide mass

Velikyan, Irina; Sundin, Anders; Eriksson, Barbro; Lundqvist, Hans; Sörensen, Jens; Bergström, Mats; Långström, Bengt

doi:10.1016/j.nucmedbio.2009.11.008

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 3 , Pages 265-275, April 2010

In vivo binding of [⁶⁸Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours — impact of peptide mass

Irina Velikyan
- Department of Biochemistry and Organic Chemistry, BMC, Uppsala University, Box 599, SE-751 24 Uppsala, Sweden
- Uppsala Applied Science Lab, GEMS PET Systems, GE Healthcare, SE-752 28 Uppsala, Sweden
Anders Sundin
- Department of Radiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Barbro Eriksson
- Department of Endocrine Oncology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
Hans Lundqvist
- Department of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala, Sweden
Jens Sörensen
- Department of Medicinal Sciences, Clinical Physiology and Nuclear Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
Mats Bergström
- Department of Pharmaceutical Biosciences, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden
Bengt Långström
- Department of Biochemistry and Organic Chemistry, BMC, Uppsala University, Box 599, SE-751 24 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.

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.

Keywords: ⁶⁸Ga, Specific radioactivity, Octreotide, PET, [⁶⁸Ga]-DOTATOC, Neuroendocrine, Somatostatin, Dosimetry