Lu-177-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10323194" target="_blank" >RIV/00216208:11310/16:10323194 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1186/s13550-016-0161-3" target="_blank" >http://dx.doi.org/10.1186/s13550-016-0161-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13550-016-0161-3" target="_blank" >10.1186/s13550-016-0161-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lu-177-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment

Popis výsledku v původním jazyce

Metastatic bone lesion is a common syndrome of many cancer diseases in an advanced state. Common treatments including systemic application of bisphosphonate drugs aim on pain reduction and on improving the quality of life of the patient. Particularly, patients with multiple metastatic lesions benefit from bone-targeting therapeutic radiopharmaceuticals. No-carrier-added Lu-177 is remarkably suitable for an application in this scope. Five DOTA-and DO2A-based bisphosphonates, including monomeric and dimeric structures and one NO2A-derivative, were synthesized and labelled with Lu-177. Radiolabelling yields for [Lu-177]Lu-DOTA and [Lu-177]Lu-NO2A monomeric bisphosphonate complexes were >98 % within 15 min. The dimeric macrocyclic bisphosphonates showed a decelerated labelling kinetics, reaching a plateau after 30 min of 60 to 90 % radiolabelling yields. All Lu-177-bisphosphonate complexes showed exclusive accumulation in the skeleton. Blood clearance and renal elimination were fast. SUV data (all for 1 h p.i.) in the femur ranged from 3.34 to 5.67. The bone/blood ratios were between 3.6 and 135.6, correspondingly. Lu-177-bisphosphonate dimers showed a slightly higher bone accumulation (SUVfemur = 4.48 +/- 0.38 for [Lu-177] Lu-DO2A(P-BP)(2); SUVfemur = 5.41 +/- 0.46 for [Lu-177]Lu-DOTA(M-BP)(2)) but a slower blood clearance (SUVblood = 1.25 +/- 0.09 for [Lu-177]Lu-DO2A(P-BP)(2); SUVblood = 1.43 +/- 0.32 for [Lu-177]Lu-DOTA(M-BP)(2)). Conclusions: Lu-complexes of macrocyclic bisphosphonates might become options for the therapy of skeletal metastases in the near future, since they show high uptake in bone together with a very low soft-tissue accumulation.

Název v anglickém jazyce

Lu-177-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment

Popis výsledku anglicky

Metastatic bone lesion is a common syndrome of many cancer diseases in an advanced state. Common treatments including systemic application of bisphosphonate drugs aim on pain reduction and on improving the quality of life of the patient. Particularly, patients with multiple metastatic lesions benefit from bone-targeting therapeutic radiopharmaceuticals. No-carrier-added Lu-177 is remarkably suitable for an application in this scope. Five DOTA-and DO2A-based bisphosphonates, including monomeric and dimeric structures and one NO2A-derivative, were synthesized and labelled with Lu-177. Radiolabelling yields for [Lu-177]Lu-DOTA and [Lu-177]Lu-NO2A monomeric bisphosphonate complexes were >98 % within 15 min. The dimeric macrocyclic bisphosphonates showed a decelerated labelling kinetics, reaching a plateau after 30 min of 60 to 90 % radiolabelling yields. All Lu-177-bisphosphonate complexes showed exclusive accumulation in the skeleton. Blood clearance and renal elimination were fast. SUV data (all for 1 h p.i.) in the femur ranged from 3.34 to 5.67. The bone/blood ratios were between 3.6 and 135.6, correspondingly. Lu-177-bisphosphonate dimers showed a slightly higher bone accumulation (SUVfemur = 4.48 +/- 0.38 for [Lu-177] Lu-DO2A(P-BP)(2); SUVfemur = 5.41 +/- 0.46 for [Lu-177]Lu-DOTA(M-BP)(2)) but a slower blood clearance (SUVblood = 1.25 +/- 0.09 for [Lu-177]Lu-DO2A(P-BP)(2); SUVblood = 1.43 +/- 0.32 for [Lu-177]Lu-DOTA(M-BP)(2)). Conclusions: Lu-complexes of macrocyclic bisphosphonates might become options for the therapy of skeletal metastases in the near future, since they show high uptake in bone together with a very low soft-tissue accumulation.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CA - Anorganická chemie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EJNMMI Research

ISSN

2191-219X

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

neuveden

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000369486700002

EID výsledku v databázi Scopus

2-s2.0-84954458116