Intraoperative scintigraphic detection of abdominal endocrine tumors : Development and evaluation of hand held gamma sensitive probes for¹¹¹In

Abstract: Surgery of endocrine tumors benefit from accurate pre and- intraoperative localization methods,and scintigraphy has become an important contribution in this respect. In the present thesis therequisites for scintigraphic localization of abdominal endocrine tumors and new detectors forintraoperative gammadetection are evaluated.Ac5 is a monoclonal murine antibody developed against human adrenocortical carcinoma. In a nude mouse experimental model, the radiolabeled antibody and its Fab´2 fragment were evaluated after grafting of two human adrenocortical carcinoma cell-lines (SW 13, T-CAR1). During scintigraphy of grafted animals, tumors were visualized especially with the fragmented antibody. The Ac5 antibody/Fab2 fragment may become a diagnostic tool for detection of adrenocortical carcinoma.The somatostatin analogue [111In]-DTPA-D-[Phe1]-octreotide (OctreoScan®) has been shown to visualize endocrine tumors with scintigraphy. The biodistribution of [111In]-DTPA-D-[phe1]-octreotide was studied by use of operative biopsies. Mid-gut carcinoids and endocrine pancreatic tumors of patients exposed to [111In]-DTPA-D-[Phe1]-octreotide, revealed high uptake in tumors with a tumor-to-blood ratio up to 2000. After preoperative single photon emission computerized tomography (SPECT), commercially available hand-held gammasensitive probes were used for intraoperative detection of tumors. These detectors were found to be insufficient in the abdomen mainly because of poor adaptation to the high background activity of 111In. A novel detector, H-probe2 was constructed. It was found to detect even tiny tumors, lesions inaccessible to surgical palpation upon ex vivo scanning of operative specimens. In vivo, H-probe2 detected smaller tumors than preoperative SPECT, but the scanning procedure was too time consuming for surgical applicability. Further development resulted in Matris 16, a computerized 16 channel detector for intraoperative use in combination with [111In]-DTPA-D-[Phe1]-octreotide. Matris 16 demonstratedsubstantial sensitivity and spatial resolution. It had the ability to detect abdominal endocrine tumorsmeasuring down to a few mm both in vivo and ex vivo. By allowing faster scanning with preserved sensitivity Matris 16 can improve the intraoperative tumor detection of endocrine neoplasms.