Design of a radiopharmaceutical for the palliation of painful bone metastases: rhenium‐186‐labeled bisphosphonate derivative

Abstract

SummaryTo develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we designed a

In Vivo Evaluation of a Radiogallium-Labeled Bifunctional Radiopharmaceutical, Ga-DOTA-MN2, for Hypoxic Tumor Imaging

“…8) Bifunctional radiopharmaceuticals have the recognition site of the molecular target and the chelation site for the radiometal independently in one molecule. [9][10][11][12] Ga-DOTA-MN2 containing two metronidazole moieties was designed in support of the previous crystallographic findings that the four nitrogens of the cyclen ring and two oxygens of the opposite carboxyl groups are coordinated to the gallium metal. 13) As expected,…”

Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics

“…[ 99 m Tc] Tc-MDP and [ 99 m Tc] Tc-HMDP have not yet been optimized from a chemical and pharmaceutical perspective because these complexes are not well-defined single-chemical species but rather mixtures of short-chain and long-chain oligomers. 9,14) Moreover, the phosphonate groups in [ 99 m Tc] Tc-MDP and [ 99 m Tc] Tc-HMDP are used both as ligands for coordination and as carriers to hydroxyapatite (HA) in bone, 15) which may decrease the inherent affinity of MDP and HMDP for bone. To overcome these drawbacks, a more logical design strategy has been proposed on the basis of the conjugation of a stable radiometal complex with a carrier molecule to bone.…”

Design of Ga–DOTA-based bifunctional radiopharmaceuticals: Two functional moieties can be conjugated to radiogallium–DOTA without reducing the complex stability

“…As positron-emitters for PET, 11 C, 13 N, 15 O and 18 F have been widely used, but their physical half-lives are very short ( 11 C: 20.39 min, 13 N: 9.96 min, 15 O: 122 s, 18 F: 109.8 min). Thus, the use of PET requires large-scale and expensive equipment such as an on-site cyclotron for the production of the short-lived positron-emitters, radiochemistry systems for the synthesis of PET tracers, and incidental equipment, limiting the availability of PET imaging.…”

“…Bifunctional radiopharmaceuticals have the recognition site of the molecular target and chelation site for the radiometal independently in one molecule. [13][14][15][16] In the present study, we designed and synthesized 2,2 0 -[4,10-bis(2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]amino}-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl]diacetic acid ( Fig. 1, DOTA-MN2), employing a metronidazole moiety as the recognition site of hypoxic lesions.…”