Superscript68/SuperscriptGallium and Supersc

Authors: Rudolf A Werner Christina Bluemel Martin S AllenAuerbach Takahiro Higuchi Ken Herrmann

Publish Date: 2014/08/20

Volume: 29, Issue: 1, Pages: 1-7

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Abstract

Abundant expression of somatostatin receptors SSTR is frequently identified in differentiated neuroendocrine tumors and may serve as potential target for diagnostic imaging and treatment This article discusses the “theranostic approach” of SSTRtargeting compounds including an overview of its role for diagnosis staging and restaging discussing its way to being established in clinical routine and giving an outlook about further potentially relevant developmentsRecent developments in cancer research have resulted in a wide spectrum of therapies Due to the large heterogeneity of patients and tumors there is an increasing demand for personalized medicine Introduction of the theranostic approach is based on the idea of selecting patients through a diagnostic study indicating whether a patient will benefit from a therapy or notThe theranostic principle has been applied in the field of nuclear medicine for more than 60 years and 131I and 89Sr are still established in daily clinical routine 131I was first discovered in 1938 by Seaborg and Livingood at the University of California Berkeley Already in 1946 Seidlin et al 1 reported the therapeutic use of 131I for patients with metastasized adenocarcinoma of the thyroid Since then the combination of radiolabeled iodine for diagnostic imaging and therapy represents an established and accepted “theranostic” approach In 1942 Pecher demonstrated that 89Sr accumulates in bone tumors in animals and later these findings were translated to humans and 89Sr was widely used in cancer patients 2 3 More recently a number of new theranostic approaches have been introduced including 123I/131Ilabeled Metaiodobenzylguanidine MIBG for diagnosis and treatment of neuroblastoma 4 5 6 An additional theranostic pair consisting of 123I and 131Imetomidate for diagnosis and treatment of adrenocortical carcinomas ACC has been established at the University Hospital of Würzburg The diagnostic scan with 123Imetomidate allows for the prediction whether an ACC patient will benefit from 131Imetomidate radionuclide therapy after determination of an individualized dose by dosimetry 7 8 First clinical data revealed tumor control in half of the patients undergoing 131Imetomidate therapy 7 9In this article we focus on the recently introduced and clinically translated “theranostic approach” of somatostatin receptor SSTR targeting compounds for treatment of patients with neuroendocrine tumors NETs We will present an overview of its role for diagnosis staging and restaging discussing its way to being established in clinical routine and giving an outlook about new developments69yearold male suffering from Ileum NET primary tumor with paraaortal thoracic lymph node metastases Left pretherapeutic 68GaDOTATOC PET/CT anterior view transaxial view showing primary tumor ileum and paraaortal mediastinal lymph node metastases Right posttherapeutic fused SPECT/CT after administering 74 GBq 177LuDOTATATE showing prominent uptake in the primary tumor and paraaortal thoracic lymph node metastasesThe rationale of this theranostic approach bases on the fact that welldifferentiated NETs usually overexpress SSTR on their tumor cell surface which may serve as diagnostic and therapeutic targets 10 Five different membranebound receptors have been evaluated SSTR1 SSTR2 SSTR3 SSTR4 and SSTR5 Out of these potential targets usually SSTR2 is addressed for diagnosis and therapy Using radiolabeled somatostatin analogs for functional imaging the diagnosis of NETs can be confirmed and the tumor burden metastases assessed These nuclear medicine imaging procedures provide essential information about SSTR density which is relevant for treatment decisions and selecting patients for treatment with peptide receptor radionuclide therapy PRRT 11 In general PRRT is recommended in inoperable metastasized cases expressing SSTR on tumor cell surface 12111InDTPAoctreotide binding to SSTR2 was the first and most widely used radiopharmaceutical for detecting and staging NETs 13 Planar images should be performed and if available single photon emission computed tomography SPECT after 4 and 24 h 14 With an overall sensitivity of 80  111InDTPAoctreotide scintigraphy including SPECT seems to be an effective method to detect tumor burden 15 However reduced detection rate has been reported in small and deepseated lesions even when using hybrid SPECT/CT scanners 16 Historically verified 111In can not only be used for diagnosis and staging of NETs but also for treatment treating 40 patients by using the Auger electron emitting radionuclide 111In partial remission PR was reported in one patient minor remission in six patients and stable disease SD in 14 patients 17 In another study only two of 27 patients 8  showed imagingbased morphological PR 18 Due to the short particle range and the resulting limited tissue penetration tumor regression only rarely occurred 19

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