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Rivista di Medicina Nucleare e Imaging Molecolare

A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the Society of Radiopharmaceutical Sciences and to the International Research Group of Immunoscintigraphy
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The Quarterly Journal of Nuclear Medicine 1999 June;43(2):170-6

lingua: Inglese

Dying a thou­sand ­deaths. Radionuclide imag­ing of apop­to­sis

Blankenberg F., Ohtsuki K., Strauss H. W.

From the Department of Radiology and Division of Nuclear Medicine Stanford University School of Medicine, Stanford, CA, USA


Programmed ­cell ­death, apop­to­sis, is an indu­cible, orga­nized, ener­gy requir­ing ­form of ­demise ­that ­results in the dis­ap­pear­ance of a ­cell with­out the induc­tion of an inflam­ma­to­ry ­response. Apoptotic ­cell ­death is strik­ing­ly dif­fer­ent ­than necrot­ic ­death, ­which is dis­or­der­ly, ­does not ­require ener­gy and ­results in ­local inflam­ma­tion, usu­al­ly sec­on­dary to sud­den ­release of intra­cel­lu­lar con­tents. Apoptosis is ­induced ­when ­cells under­go ­severe inju­ry to ­their nucle­us, as ­occurs fol­low­ing expo­sure to gam­ma or X-radi­a­tion, or mit­co­chon­dria, as ­occurs in a varie­ty of ­viral ill­ness­es. Apoptosis can ­also be ­induced by exter­nal sig­nals, ­such as inter­ac­tion of fas ­ligand ­with fas recep­tors. Once the ­cell is com­mit­ted to apop­to­sis, the cas­pase ­enzyme cas­cade is acti­vat­ed. An ear­ly ­effect of cas­pase acti­va­tion is the rap­id expres­sion of phos­phat­i­dyl­se­rine on the exter­nal leaf­let of the ­cell mem­brane. Membrane ­bound phos­phat­i­dyl­se­rine expres­sion ­serves as a sig­nal to sur­round­ing ­cells, iden­ti­fy­ing the express­ing ­cell as under­go­ing apop­to­sis. A defi­cien­cy or an ­excess of pro­grammed ­cell ­death is an inte­gral com­po­nent of auto­im­mune dis­or­ders, trans­plant rejec­tion and can­cer. A tech­nique to ­image pro­grammed ­cell ­death ­would be use­ful to ­assist in the devel­op­ment of ­drugs ­designed to ­treat ­these dis­eas­es, and to mon­i­tor the effec­tive­ness of ther­a­py. The sud­den expres­sion of phos­phat­i­dyl­se­rine on the ­cell mem­brane is a tar­get ­that ­could be ­used for ­this pur­pose. A 35 kD phys­io­log­ic pro­tein, Annexin V lip­o­cor­tin, ­binds ­with nano­mo­lar affin­ity to mem­brane ­bound phos­phat­i­dyl­se­rine. Annexin V has ­been radio­lab­eled ­with Technetium-99m by ­direct ­coupling to ­free sulf­hy­dryl ­groups, and ­through the hydra­zin­o­nic­a­tin­a­mide and N2S2 link­ing ­agents. The bio­dis­trib­u­tion of the ­agents ­labeled ­with ­each of the meth­ods is slight­ly dif­fer­ent. In all cas­es the radio­phar­ma­ceu­ti­cal ­binds to ­cells under­go­ing apop­to­sis in vitro, and per­mits imag­ing of the pro­cess in experi­men­tal ani­mals.

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