ORIGINAL ARTICLES  RADIOPHARMACOLOGY 

The Quarterly Journal of Nuclear Medicine 2003 September;47(3):189-99

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Radiotracer-based strategies to image angiogenesis

Haubner R. H., Wester H. J., Weber W. A., Schwaiger M.

Department of Nuclear Medicine Klinikum rechts der Isar Technische Universität München, Munich, Germany

Tumour-­induced angio­gen­e­sis ­plays an impor­tant ­role in ­tumour pro­gres­sion. Great ­efforts are ­made to devel­op ther­a­peu­tic strat­e­gies to inter­fere ­with ­this pro­cess result­ing in the star­va­tion of the ­tumour. However, strat­e­gies to mon­i­tor con­ven­tion­al ther­a­pies ­seems to be inap­pro­pri­ate to con­trol ­these approach­es. Thus, ­there is a ­keen inter­est in devel­op­ing meth­ods sup­ply­ing infor­ma­tion ­about the cor­re­spond­ing ther­a­peu­ti­cal ­effects. Several radio­trac­er-­based approach­es ­focused on dif­fer­ent tar­gets in the angio­gen­ic pro­cess are cur­rent­ly inves­ti­gat­ed. One ­class of trac­ers is ­based on ­matrix met­al­lop­ro­tei­nas­es inhib­i­tors. These com­pounds ­show prom­is­ing ­results in in ­vitro ­assays. However, ­initial ­data ­from in ­vivo stud­ies ­using ­murine ­tumour mod­els ­could not con­firm suc­cess­ful non-inva­sive mon­i­tor­ing of MMP activ­ity yet. Another strat­e­gy ­uses a radio­lab­elled sin­gle ­chain frag­ment ­against the ED-B ­domain of fibro­nec­tin, an extra­cel­lu­lar ­matrix pro­tein. Promising ­results dem­on­strat­ed selec­tive accu­mu­la­tion of the trac­er in the ­tumour vas­cu­la­ture of a ­murine ­tumour mod­el. Most of the stud­ies are con­cen­trat­ed on the devel­op­ment of radio­lab­elled antag­o­nists of the inte­grin αvβ3. This het­er­o­di­mer­ic trans­mem­brane gly­co­pro­tein is ­involved in the migra­tion of acti­vat­ed endo­the­lial ­cells dur­ing for­ma­tion of new ves­sels. Different com­pounds ­have ­been ­labelled ­with 18F, 111In, 99mTc, 90Y and sev­er­al ­iodine iso­tops. In in ­vitro ­assays ­most of ­them ­revealed ­high αvβ3 affin­ity and selec­tiv­ity. Moreover, in dif­fer­ent ­murine ­tumour mod­els suc­cess­ful non-inva­sive deter­mi­na­tion of αvβ3 expres­sion has ­been ­shown. Some of ­these approach­es indi­cate ­that ­tumour-­induced angio­gen­e­sis can be mon­i­tored in ani­mal stud­ies. Nevertheless, trans­la­tion of ­these approach­es ­into clin­i­cal set­tings allow­ing vis­u­al­isa­tion of ­tumour-­induced angio­gen­e­sis in ­patients ­needs ­still to be dem­on­strat­ed.