Use of PET in neuroendocrine tumors - In vivo applications and in vitro studies

Positron emission tomography (PET) performed with various radiolabelled com pounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, i t is also possible to localize the tumor. In initial studies, F-18-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metab olism in cancerous tissue. However, this tracer was not to any significant degree taken up by the neuroendocrine tumors. Instead, the serotonin precur sor 5-hydroxytryptophan (5-HTP) labeled with C-11 was used and showed an in creased uptake and irreversible trapping of this tracer in carcinoid tumors . The uptake was selective and the resolution so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide sc intigraphy. One problem was, however, the high renal excretion of the trace r producing streaky artifacts in the area of interest. Using the decarboxyl ase inhibitor carbidopa, given as peroral premedication, the renal excretio n decreased 6-fold and at the same time the tumor uptake increased S-fold, hence improving the visualization of the tumors. When patients were followe d during treatment with PET using 5-HTP as a tracer, a >95% correlation bet ween changes in urinary 5-hydoxyindoleacetic acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5-HIAA is considered to be unc ommon in endocrine pancreatic tumors (EPTs). Initially, C-11-labeled L-DOPA was attempted as another amine important in the APUD system. With L-DOPA a bout half of the EPTs, mainly functioning tumors, could be detected. Recent ly, 5-HTP was explored as a universal tracer also for EPT and foregut carci noids, extending the PET-examination to both thorax and abdomen (whole-body PET-examination). With this method we were able to visualize small lesions in the pancreas and thorax(e.g. ACTH-producing bronchial carcinoids) not d etectable by any other method including octreotide scintigraphy, MRI and CT . Several other tracers have been investigated, e.g. the monoamineoxidase ( MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enz ymes and receptors, both for neurotransmitters and for peptides and protein s in in vitro assays with the potential to use some of the developed tracer s for in vivo visualization and tumor biological studies. In conclusion, PE T is a valuable tool in the diagnosis of neuroendocrine tumors. It can dete ct small lesions in the thorax and abdomen not detected by other methods, w hich has been of great value preoperatively in several cases. It detects mo re lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.