Intraindividual Comparison of Selective Arterial versus Venous 68Ga-DOTATOC PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors

Abstract

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...

Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC

“…However, other positron emiting radionuclides are recommended such as 18 F-fluorodopamine, and, the most widely used, 68 Ga-labeled peptides. In spite of superior resolution, short imaging time and imaging whole body in three dimensions, the price and availability of use of this pharmaceuticals still do not allow wide application [36,37].…”

Hepatic arterial infusion enhances DOTATOC radiopeptide therapy in patients with neuroendocrine liver metastases

“…injection of MBq 68 Ga-DOTATOC. The synthesis of the tracer has already been described previously (Kratochwil et al 2010). Static emission scans, corrected for dead time, scatter, and decay were acquired from the vertex to the proximal legsrequiring eight bed positions, 4 min each.…”

“…administration led to a 3.7-fold higher tumor accumulation compared with i.v. infusion (Kratochwil et al 2010) in the early-uptake phase. However, due to the short half-life of unclear if redistribution effects would decrease the observed improvement over time and therefore, if the i.a.…”

Diagnosis and therapy are walking together on radiopeptides’ avenue

“…Comparative semiquantitative dose estimates were recently demonstrated by the Heidelberg group using 68 Ga-DOTATOC PET [29]. In this study, the authors demonstrate that SST analogues show a 3.75-fold higher standardized uptake value (SUV) in liver metastases after i.a.…”