[111In-DTPA]octreotide Tumor Uptake in GEPNET Liver Metastases After Intra-Arterial Administration: An Overview of Preclinical and Clinical Observations and Implications for Tumor Radiation Dose After Peptide Radionuclide Therapy

Stefan E. Pool, Boen L.R. Kam, Gerben A. Koning, Mark Konijnenberg, Timo L.M. ten Hagen, Woulter A.P. Breeman, Eric P. Krenning, Marion de Jong, Casper H.J. van Eijck
2014 Cancer Biotherapy and Radiopharmaceuticals  
Aims: With the aim to improve peptide receptor radionuclide therapy effects in patients with gastroenteropancreatic neuroendocrine tumor (GEPNET) liver metastases we explored the effect of intra-arterial (IA) administration of [ 111 In-DTPA]octreotide ( 111 In-DTPAOC) on tumor uptake in an animal model and in a patient study. Methods: Preclinical study: After administering 111 In-DTPAOC intra-venously (IV) or IA, biodistribution studies were performed in rats with a hepatic somatostatin
more » ... subtype 2 (sst 2 )-positive tumor. Clinical study: 3 patients with neuroendocrine liver metastases were injected twice with 111 In-DTPAOC. The first injection was given IV, and 2 weeks later, the second was injected IA (hepatic artery). Planar images of the abdomen were made up to 72 hours after injection. Blood samples were taken and urine was collected. Pharmacokinetic modeling was performed on the IV and IA data of the same patient. Based on this model, additional 177 Lu dosimetry calculations for IV and IA administrations were performed. Results: The preclinical study showed a two-fold higher 111 In-DTPAOC tumor uptake after IA administration than after IV injection. Patient data showed a large variability in radioactivity increment in liver metastases after IA administration compared with IV administration. Renal radioactivity was not significantly lower after IA administration; 177 Lu dosimetry simulations in 1 patient using a maximum kidney radiation dose of 23 Gy showed IA administration resulted in a mean increase in tumor radiation dose of 2.9-fold. Conclusion: Preclinical and clinical data both indicate that IA administration of radiolabeled somatostatin analogs via the hepatic artery can significantly increase radionuclide uptake in GEPNET, sst 2 -positive, liver metastases up to 72 hours postinjection, although the effect of IA administration can differ between patients.
doi:10.1089/cbr.2013.1552 pmid:24820805 fatcat:iznamtropzbl3ci4njj74gsbpa