RADIOPHARMACOLOGY 

The Quarterly Journal of Nuclear Medicine 2001 June;45(2):189-200

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Imaging tumors with peptide-based radioligands

Behr T. M., Gotthardt M., Barth A., Béhé M.

From the Department of Nuclear Medicine of the Philipps-University of Marburg, Marburg, Germany

Reg­u­la­tory pep­tides are ­small, ­readily dif­fus­able and ­potent nat­ural sub­stances ­with a ­wide spec­trum of ­receptor-medi­ated ­actions in ­humans. ­High ­affinity recep­tors for ­these pep­tides are (­over-) ­expressed in ­many neo­plasms, and ­these recep­tors may rep­re­sent, there­fore, new molec­ular tar­gets for ­cancer diag­nosis and ­therapy. ­This ­review ­aims to ­give an over­view of the pep­tide-­based radio­phar­ma­ceu­ti­cals ­which are pres­ently ­already com­mer­cially avail­able or ­which are in ­advanced ­stages of ­their clin­ical ­testing so ­that ­their ­broader avail­ability is antic­i­pated ­soon. Phys­io­log­i­cally, ­these pep­tides ­bind to and act ­through G pro­tein-cou­pled recep­tors in the ­cell mem­brane. His­tor­i­cally, som­a­tos­tatin ana­logs are the ­first ­class of ­receptor ­binding pep­tides ­having ­gained clin­ical appli­ca­tion. 111In-­DTPA-[D-Phe1]-octre­o­tide is the ­first and ­only radio­pep­tide ­which has ­obtained reg­u­la­tory ­approval in ­Europe and the ­United ­States to ­date. Exten­sive clin­ical ­studies ­involving sev­eral thou­sands of ­patients ­have ­shown ­that the ­major clin­ical appli­ca­tion of som­a­tos­tatin ­receptor scin­tig­raphy is the detec­tion and the ­staging of gas­troen­te­rop­an­creatic neu­ro­en­do­crine ­tumors (car­ci­noids). In ­these ­tumors, octre­o­tide scin­tig­raphy is ­superior to any ­other ­staging ­method. How­ever, its sen­si­tivity and accu­racy in ­other, ­more fre­quent neo­plasms is lim­ited. Radio­lab­eled vasoac­tive intes­tinal pep­tide (VIP) has ­been ­shown to vis­u­alize the ­majority of gas­troin­tes­tinal adeno-­car­cin­omas, as ­well as ­some neu­ro­en­do­crine ­tumors, ­including insu­lin­omas (the ­latter ­being ­often ­missed by som­a­tos­tatin ­receptor scin­tig­raphy). Due to the out­standing diag­nostic accu­racy of the pen­ta­gas­trin ­test in ­detecting the pres­ence, per­sis­tence, or recur­rence of medul­lary thy­roid ­cancer (MTC), we pos­tu­lated the expres­sion of the cor­re­sponding (i.e. chol­e­cys­tok­inin [CCK-] -B) ­receptor ­type in ­human MTC. ­This ­receptor is ­also ­widely ­expressed on ­human ­small-­cell ­lung ­cancer. ­Indeed, 111In-­labeled ­DTPA deriv­a­tives of gas­trin ­showed excel­lent tar­geting of CCK-B ­receptor ­expressing tis­sues in ani­mals and ­patients. A ­variety of fur­ther pep­tide-­based radio­lig­ands, e.g. ­among ­many ­others, gas­trin-­releasing pep­tide/bom­besin, neu­ro­tensin, sub­stance-P, pan-som­a­tos­tatin (som­a­tos­tatin deriv­a­tives ­which ­bind to all ­five ­receptor sub­types) or glu­cagon-­like pep­tide-1 (glp-1) ana­logs (the ­latter for the spe­cific detec­tion of insu­lin­omas), is cur­rently ­under devel­op­ment. Sum­mar­izing, radio­lab­eled reg­u­la­tory pep­tides ­have ­opened new hori­zons in ­nuclear ­oncology for diag­nosis (and poten­tial ­internal radio­nu­clide ­therapy). ­Future ­work ­will prob­ably ­reveal a mul­ti­tude of ­novel poten­tially clin­i­cally ­useful pep­tide-­based radio­lig­ands.