Lu is accepted for the palliative treatment of unresectable neuroendocrine cancer. However, the optimal route of administration has not been determined. Using positron-emission tomography (PET)-labeled 68 Ga-DOTATOC, we compared selective tumoral uptake on PET/computed tomography (CT) after arterial or venous administration of the agent in patients with gastroenteropancreatic neuroendocrine tumor. Experimental Design: Fifteen patients with neuroendocrine cancer were examined with 68 Ga-DOTA-TOC PET/CT after intravenous (i.v.) and intraarterial (i.a.) administration within 4 weeks of each other and without any intervening therapy. Eleven patients had multifocal metastases, six were considered to have unresectable primary tumor. The intraarterial catheter was placed in the vessel supplying the main tumor burden. The standard uptake value (SUV) was used to compare intratumoral concentrations of 68 Ga-DOTATOC. Results: Compared with i.v. infusion, the i.a. infusion resulted in an increased SUV in 117 of 122 (96%) liver metastases. The average increase in SUV was 3.75-fold higher with i.a. administration. The increase in uptake for the primary tumors was dependent on the selectivity of the catheter placement, resulting in variable increases in SUV after i.a. injection (1.44-to 7.8-fold higher).Conclusions: This study showed that uptake of DOTATOC is commonly several fold higher after selective i.a. administration in comparison with i.v. injection in both the primary tumor as well as in liver metastases of neuroendocrine cancer. Therefore, intraarterial DOTATOC is a promising drug for regionally intensified radiopeptide therapy. Clin Cancer Res; 16(10); 2899-905. ©2010 AACR.There are few effective treatments for unresectable, well differentiated, disseminated gastroenteropancreatic neuroendocrine tumor (GEP-NET). Although the progression rate was slower than with many solid tumors, NETs also showed poor response to conventional chemotherapy with objective response rates in the range of 10% to 36% (1, 2). Antiproliferative therapy with octreotide or IFN could stabilize disease for ∼8 months (mean), as recently shown in the PROMID study (3). However, tumor shrinkage occurs in <10%. NETs commonly metastasize to the liver, and regional treatments such as radiofrequency ablation, transarterial chemoembolization, and selective internal radiation therapy have been used in this setting. However, radiofrequency ablation suffers from high recurrence rates (4); whereas transarterial chemoembolization and selective internal radiation therapy are contraindicated in cases of complete portal vein thrombosis or hepatic insufficiency. Additionally, postembolization syndrome is often observed and the effect on survival has yet to be proven in larger clinical trials (5). These treatments are also not generally suitable for metastases outside the liver (2).Although selective internal radiation therapy provides regional untargeted radiation therapy to the liver, peptides targeting the somatostatin receptor, which is frequently overexpress...

Intravenously administered radiolabeled peptides targeting somatostatin receptors are used for the treatment of unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Recently, we demonstrated a high first-pass effect during intra-arterial (i.a.) administration of positron emission tomography (PET) labeled Lu-DOTATOC were infused into the hepatic artery of 15 patients with liver metastases arising from GEP-NETs. Response was assessed using DOTATOC-PET, multiphase contrast enhanced computed tomography, magnetic resonance imaging, and the serum tumor marker chromogranin A. Pharmacokinetic data of the arterial approach were assessed using 111In-DOTATOC scans. With the treatment regime of this pilot study, complete remission was achieved in one (7%) patient and partial remission was observed in eight (53%) patients, six patients were classified as stable (40%; response evaluation criteria in solid tumors criteria). The concomitant decrease of elevated serum tumor marker confirmed the radiologic response. Median time to progression was not reached within a mean follow-up period of 20 months. Receptor saturation and redistribution effects were identified as limiting factors for i.a. DOTATOC therapy. The high rate of objective radiologic response in NET patients treated with arterial infusion of 90 Y-/ 177 Lu-DOTATOC compares favorably with systemic chemotherapy and intravenous radiopeptide therapy. While i.a. DOTATOC therapy is only applicable to patients with tumors of limited anatomic distribution, the results of this pilot study are a promising development in the treatment of GEP-NET and warrants further investigation of this novel approach.

Complications of embolization and chemoembolization remain a problem even with the development of low-profile catheter material and the introduction of new embolization agents. In recent years many new embolization materials have become available for clinical use, so the possibilities and limitations of these new materials must be understood to allow safe and effective embolization. Although up to now some scientific work has been published reporting the basic risk of embolization procedures, the underlying pathomechanism remains the object of speculation. Besides complications like drug toxicity, allergic reactions, and bleeding of the puncture site, the characteristics of embolization materials must be known to understand the potential complications of nontarget embolization and reflux of embolization material. This article gives an overview of established and new embolization materials, their potential risks, and the underlying pathophysiology.