Vasoactive intestinal peptide receptor scintigraphy in patients with pancreatic adenocarcinomas or neuroendocrine tumours

Human adenocarcinomas of the gastroenteropancreatic system overexpress vaso active intestinal peptide (VIP) receptors and therefore represent logical d iagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy ( VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic t umours, in almost all cases. So far, however, only a single centre has demo nstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic m etastatic adenocarcinomas and neuroendocrine tumours, VIP was radiolabelled with carrier-free I-123 using the chloramine T-method and preparative high -performance liquid chromatography for purification. Patients with metastat ic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radio iodinated VIP of maximum specific radioactivity maintained a high biologica l activity as determined by cAMP formation in receptor-expressing tumour ce ll lines. Intravenous injection of I-123-VIP did not cause any side-effects . Biodistribution, determined over 24 h. was high in the lungs and low in a bdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primarie s or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the pri mary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand recep tor autoradiography and shown to be receptor positive. Moreover, in vitro r eceptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver, It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous a dministration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retr ospect, these findings are not surprising since VIP receptor expression was observed to be higher in normal tissues than in neoplastic ones.