ENDOCRINOLOGY - II
Therapy 

The Quarterly Journal of Nuclear Medicine 1999 December;43(4):356-66

Copyright © 2000 EDIZIONI MINERVA MEDICA

lingua: Inglese

Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues

De Jong M., Breeman W. A. P., Bernard H. F., Kooij P. P. M., Slooter G. D.*, Van Eijck C. H. J.*, Kwekkeboom D. J., Valkema R., Macke H. R.**, Krenning E. P.**

From the Department of Nuclear Medicine *Surgery, **Kantonspital Basel, Switzerland and ***Internal Medicine III University Hospital and Erasmus University Rotterdam, The Netherlands

Peptide recep­tor scin­tig­ra­phy ­with the radio­ac­tive som­a­tos­ta­tin-ana­logue [111In-­DTPA0]octre­o­tide (­DTPA = dieth­y­len­e­tri­a­min­e­pen­taa­cet­ic ­acid) is a sen­si­tive and spe­cif­ic tech­nique to ­show in ­vivo the pres­ence and abun­dance of som­a­tos­ta­tin recep­tors on var­i­ous ­tumors. With ­this tech­nique pri­mary ­tumors and metas­ta­ses of neu­ro­en­do­crine can­cers as ­well as of ­many oth­er can­cer ­types can be loc­al­ised. A new appli­ca­tion is the use of pep­tide recep­tor radio­nu­clide ther­a­py, admin­is­trat­ing ­high dos­es of 111In- or 90Y-­labeled octre­o­tide-ana­logues.
Preclinical. We inves­ti­gat­ed the radio­ther­a­peu­tic ­effect of 90Y- and 111In-­labeled [­DOTA0,Tyr3]octre­o­tide (­DOTA= tet­ra­az­a­cy­clo­dod­e­can­e­tet­raa­cet­ic ­acid) or [111In-­DTPA0]octre­o­tide in Lewis ­rats bear­ing the som­a­tos­ta­tin recep­tor-pos­i­tive rat pan­creat­ic ­tumor CA20948 in A) the ­flank or B) in the liv­er.
Patients. Thirty end-­stage ­patients ­with most­ly neu­ro­en­do­crine pro­gress­ing ­tumors ­were treat­ed ­with [111In-­DTPA0]octre­o­tide, up to a max­i­mal cumu­la­tive ­patient ­dose of ­about 74 GBq, in a ­phase 1 ­trial.
Preclinical ­results. A) Flank mod­el: at ­least two 111MBq injec­tions of [111In-­DOTA0,Tyr3]octre­o­tide ­were need­ed to ­reach ­tumor ­response, in 40% of the ani­mals com­plete ­tumor remis­sion was ­found ­after a fol­low-up peri­od of 10 ­months. One or two injec­tions of [90Y-­DOTA0,Tyr3] octre­o­tide yield­ed tran­sient ­stable dis­ease.
B) Liv­er mod­el: we ­found ­that pep­tide recep­tor radio­nu­clide ther­a­py is ­only effec­tive if som­a­tos­ta­tin recep­tors are ­present on the ­tumors, and is there­fore recep­tor-medi­at­ed. High radio­ac­tive dos­es of 370 MBq [111In-­DTPA0]octre­o­tide or 93 MBq [90Y-­DOTA0,Tyr3]octre­o­tide can inhib­it the ­growth of som­a­tos­ta­tin recep­tor-pos­i­tive metas­ta­ses.
Clinical results. There ­were no ­major clin­i­cal ­side ­effects ­after up to 2 ­years treat­ment, ­except ­that a tran­sient ­decline in plate­let ­counts and lym­pho­cyte sub­sets can ­occur. Promising ben­e­fi­cial ­effects on clin­i­cal symp­toms, hor­mone pro­duc­tion and ­tumor pro­life­ra­tion ­were ­found. Of the 21 ­patients ­with pro­gres­sive dis­ease at base­line and who ­received a cumu­la­tive ­dose of ­more ­than 20 GBq [111In-­DTPA0]octre­o­tide, 8 ­patients ­showed sta­bil­isa­tion of dis­ease and 6 oth­er ­patients a reduc­tion in ­size of ­tumors. There is a ten­den­cy ­towards bet­ter ­results in ­patients ­whose ­tumors ­have a high­er accu­mu­la­tion of the radio­lig­and.
Conclusion. Radionuclide ther­a­py ­with octre­o­tide-deriv­a­tives is fea­sible, ­both ­with 111In and 90Y as radio­nu­clides.