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A Journal on Nuclear Medicine and Molecular Imaging

A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the Society of Radiopharmaceutical Sciences and to the International Research Group of Immunoscintigraphy
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index (SciSearch), Scopus
Impact Factor 2,413

Frequency: Quarterly

ISSN 1824-4785

Online ISSN 1827-1936


The Quarterly Journal of Nuclear Medicine 1999 June;43(2):125-31


Clinical imag­ing of mul­ti­drug resis­tance in can­cer

Del Vecchio S., Ciarmiello A.*, Salvatore M.

From the Nuclear Medicine, National Research Council CNR and Department of Biomorphological and Functional Sciences University “Federico II” *National Cancer Institute, Naples, Italy

The ­most ­well-char­ac­ter­ized mech­a­nism of mul­ti­drug resis­tance (MDR) ­involves P-gly­co­pro­tein (Pgp), a trans­mem­brane pro­tein act­ing as an ATP-depen­dent ­drug ­efflux ­pump. The rec­og­ni­tion of 99mTc-Sestamibi and oth­er lip­o­phil­ic cat­ions as trans­port sub­strates for Pgp pro­vid­ed the nec­es­sary ­tool for the clin­i­cal assess­ment of Pgp func­tion in ­patients ­with can­cer. Many clin­i­cal stud­ies ­from dif­fer­ent insti­tu­tions and ­trials includ­ing a varie­ty of malig­nan­cies indi­cate ­that ­both ­tumor ­uptake and clear­ance of 99mTc-Sestamibi are cor­re­lat­ed ­with Pgp expres­sion and may be ­used for the phe­no­typ­ic assess­ment of mul­ti­drug resis­tance. Although ­both param­e­ters may pre­dict ­tumor ­response to chem­o­ther­a­py, the extrac­tion of ­efflux ­rate con­stants ­appeared to pro­vide a ­more ­direct ­index of Pgp func­tion as com­pared to trac­er ­uptake ­ratio allow­ing to ­trace a con­tin­u­ous spec­trum of ­drug trans­port activ­ity. Preliminary stud­ies report­ed the use of MDR imag­ing ­agents to mon­i­tor the mod­ulat­ing abil­ity of rever­tant com­pounds. Although the ­results sup­port the fea­sibil­ity of ­this ­approach, the alter­a­tion of trac­er phar­ma­cok­i­net­ics ­induced by the mod­ula­tors cer­tain­ly con­sti­tutes a chal­lenge in the devel­op­ment of a sim­ple func­tion­al ­test suit­able in clin­i­cal prac­tice. The exten­sion of the ­acquired imag­ing meth­o­dol­o­gy to ­tumors ­with redun­dant intrin­sic resist­ant mech­a­nisms ­such as ­lung can­cer ­requires fur­ther inves­ti­ga­tions on the rel­a­tive con­tri­bu­tion and clin­i­cal rel­e­vance of ­each mech­a­nism. Due to the mul­ti­fac­to­ri­al ­nature of the phe­nom­e­non, the devel­op­ment of new trac­ers ­with sub­strate spec­i­fic­ity for oth­er ­known ­drug trans­port­ers ­would hope­ful­ly ­help to dis­sect the com­plex ­array of cel­lu­lar mech­a­nisms con­trib­ut­ing to treat­ment fail­ure.

language: English


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