Original article Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111 In-DTPA-D-Phe 1 -octreotide and yttrium-labelled DOTA-D-Phe 1 -Tyr 3 -octreotide Raffaella Barone a , Ste´ phan Walrand a , Mark Konijnenberg b , Roelf Valkema c , Larry K. Kvols d , Eric P. Krenning c , Stanislas Pauwels a and Franc¸ ois Jamar a Objective We estimated the absorbed doses for 111 In-DTPA-D-Phe 1 -octreotide and 90 Y-DOTA-D-Phe 1 - Tyr 3 -octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. Methods Six patients with neuroendocrine tumours underwent quantitative 111 In-DTPA-D-Phe 1 -octreotide SPECT and 86 Y-DOTA-D-Phe 1 -Tyr 3 -octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA K ) or 2 Gy to the red marrow (MAA RM ), was calculated and the resulting tumour absorbed doses were computed. Results For the MAA K the mean absorbed dose to the red marrow was lower for 90 Y-DOTA-D-Phe 1 -Tyr 3 -octreotide than for 111 In-DTPA-D-Phe 1 -octreotide (1.8 ± 0.9 Gy vs. 6.4 ± 1.6 Gy; P < 0.001). The median absorbed dose to tumours for the MAA K was two-fold higher for 90 Y-DOTA-D-Phe 1 -Tyr 3 -octreotide as compared to 111 In-DTPA-D-Phe 1 -octreotide (30.1 vs. 12.6 Gy; P < 0.05). The median absorbed dose to tumours estimated for the MAA RM was 10-fold higher for 90 Y-DOTA-D-Phe 1 - Tyr 3 -octreotide than for 111 In-DTPA-D-Phe 1 -octreotide (35.1 Gy vs. 3.9 Gy; P < 0.05). Conclusions This direct intra-patient comparison confirms that the use of 90 Y-DOTA-D-Phe 1 -Tyr 3 -octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using 111 In-DTPA-D-Phe 1 - octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation. Nucl Med Commun 29:283–290 c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Nuclear Medicine Communications 2008, 29:283–290 Keywords: dosimetry, indium, octreotide, therapy, yttrium a Centre of Nuclear Medicine, University of Louvain Medical School, Brussels, Belgium, b Tyco Healthcare, Petten, the Netherlands, c Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands and d Lee Moffitt Cancer Center, University of South Florida, Tampa, USA Correspondence to Dr Franc¸ ois Jamar, Centre of Nuclear Medicine, University of Louvain Medical School, UCL 54.30, Avenue Hippocrate, 54, B-1200 Brussels, Belgium Tel: +32 2764 2571; fax: +32 2764 5408; e-mail: francois.jamar@uclouvain.be Received 23 October 2007 Accepted 28 October 2007 Introduction The basic principle of peptide receptor radionuclide therapy is that the dose delivered to tumours is limited by the maximum dose that can be tolerated by normal tissues. In the case of therapy with radiolabelled somatostatin analogues, the kidneys and red marrow are the two major critical organs to take into account with regards to early or delayed radiotoxicity. Radiolabelled somatostatin analogues are cleared from the body to a high degree by the kidneys. Proximal tubular cells re-absorb part of the administered activity [1] and the infusion of basic amino acids is able to reduce the tubular reabsorption of the radiolabelled peptide, thereby protect- ing the kidneys during therapy [2–4]. This allows increasing the activities that can be administered. How- ever, the assessment of individual renal absorbed doses is essential to deliver the highest possible activity while keeping the absorbed dose below a certain threshold, for instance 23 Gy, as proposed by the ICRP [5]. With increasing activities, the red marrow becomes the dose-limiting organ. Various cells of the haemopoietic system may express somatostatin receptors [6] and thereby bind a radiolabelled analogue. In addition, in- vivo transchelation of the radiometal onto serum trans- ferrin could result in uptake by the red marrow [7]. During the last few years, clinical trials have been performed using 111 In-DTPA-D-Phe 1 -octreotide (Oct- reoScan111 or SomatoTher) and 90 Y-DOTA-D-Phe 1 - Tyr 3 -octreotide (OctreoTher or 90 Y-DOTATOC) to 0143-3636 c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.