A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10331080" target="_blank" >RIV/00216208:11310/16:10331080 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.nucmedbio.2016.07.009" target="_blank" >http://dx.doi.org/10.1016/j.nucmedbio.2016.07.009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.nucmedbio.2016.07.009" target="_blank" >10.1016/j.nucmedbio.2016.07.009</a>

Result language

angličtina

Original language name

A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting

Original language description

Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30%-50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated. The DOTA-bisphosphonate conjugate BPAMD was compared against the novel DOTAGA-derived albumin-binding bisphosphonate DOTAGA(428-D-Lys)M-BP (L1). The ligands were labeled with Ga-68(III) and were evaluated in in vitro binding studies to hydroxyapatite (HA) as well as to human serum albumin. The compounds were finally compared in in vivo PET and ex vivo organ distribution studies in small animals over 6 h. Binding studies revealed a consistent affinity of both bisphosphonate tracers to HA. Small animal PET and ex vivo organ distribution studies showed longer blood retention of [Ga-68]L1. [Ga-68]BPAMD is initially more efficiently bound to the bone but skeletal accumulation of the modified compound and [Ga-68]BPAMD equalized at 6 h p.i. Ratios of femur epiphyseal plate to ordinary bone showed to be more favorable for [Ga-68]L1 than for [Ga-68]BPAMD due to the longer circulation time of the new tracer. Thus, the chemical modification of BPAMD toward an albumin-binding bisphosphonate, L1, resulted in a novel PET tracer which conserves advantages of both functional groups within one and the same molecule. The properties of this new diagnostic tracer are expected to be preserved in Lu-177 therapeutic agent with the same ligand (a theranostic pair).

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CA - Inorganic chemistry

OECD FORD branch

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Project

<a href="/en/project/GA13-08336S" target="_blank" >GA13-08336S: Hybrid materials based on macrocyclic ligands for medical applications</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

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

Name of the periodical

Nuclear Medicine and Biology

ISSN

0969-8051

e-ISSN

—

Volume of the periodical

43

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

670-678

UT code for WoS article

000386987200003

EID of the result in the Scopus database

2-s2.0-84983435470