NEUROENDOCRINE TUMORS
Guest Editors: Bombardieri E. 

The Quarterly Journal of Nuclear Medicine 2000 March;44(1):68-76

Copyright © 2009 EDIZIONI MINERVA MEDICA

lingua: Inglese

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

Eriksson B., Bergström M. *, Örlefors H., Sundin A. *,**, Öberg K., Långström B. *

From the Department of Medical Sciences *Uppsala University PET-Centre **Department of Radiology University Hospital, Uppsala, Sweden

Positron emis­sion tomog­ra­phy (PET) per­formed ­with var­i­ous radio­lab­elled com­pounds facil­i­tates the ­study of ­tumor bio­chem­is­try. If the ­tumor ­uptake of an admin­is­tered trac­er is great­er ­than ­that of sur­round­ing nor­mal tis­sue, it is ­also pos­sible to local­ize the ­tumor. In ­initial stud­ies, 18F-­labeled deoxy­glu­cose (FDG) was attempt­ed to vis­u­al­ize the ­tumors, ­since ­this trac­er had ­been suc­cess­ful­ly ­used in oncol­o­gy, reflect­ing ­increased glu­cose metab­olism in can­cer­ous tis­sue. However, ­this trac­er was not to any sig­nif­i­cant ­degree tak­en up by the neu­ro­en­do­crine ­tumors. Instead, the serot­o­nin pre­cur­sor 5-hydrox­y­tryp­to­phan (5-HTP) ­labeled ­with 11C was ­used and ­showed an ­increased ­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 scin­tig­ra­phy. One prob­lem was, how­ev­er, the ­high ­renal excre­tion of the trac­er pro­duc­ing ­streaky arti­facts in the ­area of inter­est. Using the decar­box­y­lase inhib­i­tor car­bi­do­pa, giv­en as per­oral pre­med­i­ca­tion, the ­renal excre­tion ­decreased 6-­fold and at the ­same ­time the ­tumor ­uptake ­increased 3-­fold, ­hence improv­ing the vis­u­al­iza­tion of the ­tumors. When ­patients ­were fol­lowed dur­ing treat­ment ­with PET ­using 5-HTP as a trac­er, a >95% cor­re­la­tion ­between chang­es in uri­nary 5-hydrox­yin­dol­ea­cet­ic ­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 uncom­mon in endo­crine pan­creat­ic ­tumors (EPTs). Initially, 11C-­labeled L-­DOPA was attempt­ed as ­another ­amine impor­tant in the ­APUD ­system. With L-­DOPA ­about ­half of the EPTs, main­ly func­tion­ing ­tumors, ­could be detect­ed. Recently, 5-HTP was ­explored as a uni­ver­sal trac­er ­also for EPT and fore­gut car­ci­noids, 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 detect­able 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 ­enzymes and recep­tors, ­both for neu­ro­trans­mit­ters and for pep­tides and pro­teins in in ­vitro ­assays ­with the poten­tial to use ­some of the devel­oped trac­ers for in ­vivo vis­u­al­iza­tion and ­tumor bio­log­i­cal stud­ies. In con­clu­sion, PET is a val­u­able ­tool in the diag­no­sis of neu­ro­en­do­crine ­tumors. It can ­detect ­small ­lesions in the tho­rax and abdo­men not detect­ed by oth­er meth­ods, ­which has ­been of ­great val­ue pre­op­er­a­tive­ly in sev­er­al cas­es. It ­detects ­more ­lesions in the liv­er and ­lymph ­nodes ­than oth­er meth­ods and fur­ther­more, it can be ­used to mon­i­tor treat­ment ­effects.