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A Journal on Nuclear Medicine and Molecular Imaging
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ORIGINAL ARTICLES  RADIOPHARMACOLOGY


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

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


FULL TEXT  


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.

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