European Journal of Nuclear Medicine and Molecular Imaging Vol. 30, No. 1, January 2003 Abstract. Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin re- ceptor (sst) scintigraphy with PET, a novel carbohydrat- ed 18 F-labelled sst ligand was developed and preclinical- ly evaluated. Synthesis of N α -(1-deoxy-D-fructosyl)-N ε - (2-[ 18 F]fluoropropionyl)-Lys 0 -Tyr 3 -octreotate ([ 18 F]FP- Gluc-TOCA) was completed in ~3 h (20%–30% yield). [ 19 F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC 50 : 437±84 nM) and hsst5 (IC 50 : 123±8.8 nM) and very high affinity to hsst2 (IC 50 : 2.8±0.4 nM). As a result of carbohydration, lipo- philicity of [ 18 F]FP-Gluc-TOCA was found to be low (lg P OW =–1.70±0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%±1.09%ID/g) and showed low uptake in liver (0.72%±0.14%ID/g) and intestine (1.88%±0.52%ID/g) and high tumour uptake (13.54%±1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, re- spectively. A similar biodistribution pattern was ob- served in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 μg Tyr 3 -octreotide, dem- onstrating sst-specific uptake. In a first [ 18 F]FP-Gluc- TOCA-PET study of a patient with a metastatic carci- noid in the liver the tracer showed superior pharmacoki- netics, e.g. rapid urinary excretion and low uptake in liv- er, kidney and spleen. Multiple liver lesions (SUVs rang- ing from 21.4 to 38.0) and previously unknown focal up- take in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an 18 F-la- belled sst binding peptide; it indicates that [ 18 F]FP-Gluc- TOCA offers excellent imaging characteristics and al- lows sst imaging with high tumour to non-tumour con- trast. Keywords: Octreotide – Octreotate – Somatostatin – Glycation – Carbohydration – PET Eur J Nucl Med (2003) 30:117–122 DOI 10.1007/s00259-002-1012-1 Introduction Since the late 1980s, strategies for somatostatin receptor (sst) targeted imaging and therapeutic intervention have been intensively investigated. Among the sst ligands in- vestigated, [ 111 In]DTPA-octreotide has been approved for routine clinical scintigraphy of sst-expressing tu- mours and, more recently, [ 99m Tc]depreotide has been approved for the evaluation of lung carcinoma. Further- more, results obtained with sst-targeted peptide receptor radiotherapy (PRRT) are promising, and, for example, [ 90 Y]DOTA-Tyr 3 -octreotide and [ 177 Lu]DOTA-Tyr 3 -oct- reotate are being investigated in ongoing clinical radio- therapy trials. Because of the high spatial resolution of positron emission tomography (PET) and its ability to quantify biodistribution and uptake kinetics, sst ligands have also been labelled with the positron emitters 18 F (96.7% β + ), 64 Cu (17.4% β + ), 66 Ga (56% β + ), 68 Ga (89% β + ), 76 Br (55.6% β + ), 86 Y (31.9% β + ) and 124 I (22.8% β + ). The ease of peptide radiolabelling by complexation makes 68 Ga (E β + ,max =2.921 MeV, t 1/2 =67.6 min), which can be obtained from the 68 Ge/ 68 Ga generator, and 64 Cu (17.4% ß + , E β + ,max =1.673 MeV, t 1/2 =12.7 h, 39.6% β – , E β – ,max = H. J. Wester ( ✉ ) Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 München, Germany e-mail: H.J.Wester@lrz.tu-muenchen.de Tel.: +49-89-41404586, Fax: +49-89-41404841 Short communication PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18 F-labelled, carbohydrated analogue of octreotide H. J. Wester 1 , M. Schottelius 1 , K. Scheidhauer 1 , G. Meisetschläger 1 , M. Herz 1 , F. C. Rau 1 , J. C. Reubi 2 , M. Schwaiger 1 1 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 München, Germany 2 Institute of Pathology, University of Berne, Berne, Switzerland Received: 19 May 2002 / Accepted: 28 August 2002 / Published online: 5 November 2002 © Springer-Verlag 2002