Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases

Lange, Rogier; Heine, Rob ter; Knapp, Russ Ff; Klerk, John M. H. de; Bloemendal, Haiko J.; Hendrikse, N. Harry

doi:10.1016/j.bone.2016.08.002

Cited by 51 publications

(27 citation statements)

References 133 publications

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“…The simplest bone binding radiopharmaceuticals for palliative endoradiotherapy, belonging to the class of calcium mimetics, for example, 89 Sr, 32 P, and 223 Ra. Their localization underlies the same mechanisms as calcium and, therefore, may be unpredictable [9]. …”

Section: Introductionmentioning

confidence: 99%

“…The first successful clinical phase III studies showed a low haemotoxicity and prolonged survival in metastatic prostate cancer [10]. However, the consequences of the 223 Ra decay chain for the body, as well as the influence of the α-rays on the sensitive gastrointestinal tract, remain uncertain [9]. The longer half-lives of nuclides such as 89 Sr and 32 P have discouraged their use and have favored nuclides such as 153 Sm and 177 Lu with shorter half-lives and lower bone marrow toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

et al. 2017

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Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

et al. 2017

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“…A wide range of radionuclides have been investigated with such ligand systems, many of which ( 99m Tc, 68 Ga, 227 Th, 228 Ac, 212 Bi, 188 Re) are beyond the realm of this current review, but are discussed in the context of (poly)aminophosphonic acids elsewhere. 28 Specific review articles have also focused upon the targeted treatment of bone metastases using phosphonate-based ligands 29 and a broad range of radionuclides. Although not an aminophosphonic acid, the structurally simplest biphosphonic acid derivative is pyrophosphonic acid (Fig.…”

Section: Complexes Based On (Poly)aminophosphonic Acidsmentioning

confidence: 99%

Chelating agents for radiolanthanides: Applications to imaging and therapy

Amoroso

Fallis

Pope

2017

Coordination Chemistry Reviews

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“…Beside the detection of metastatic skeletal lesion by nuclear imaging, therapeutic bone‐seeking radiopharmaceuticals have been used for palliative care of pain arising from metastatic bone lesions from 1950s with 32 P being the first radionuclide proposed for this . Due to the large patient population and effectiveness of the approach, significant research was pursued in this field which led to the development of several therapeutic radiopharmaceuticals for palliation of pain due to skeletal metastases . Among these, 153 Sm‐complex of polyaminophosphonate ligand EDTMP (ethylenediaminetetramethylene phosphonic acid) has been used most extensively over the past three decades …”

Section: Introductionmentioning

confidence: 99%

Syntheses and evaluation of ⁶⁸Ga‐ and ¹⁵³Sm‐labeled DOTA‐conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases

et al. 2018

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This article reports the syntheses and evaluation of Ga- and Sm-complexes of a new DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-conjugated geminal bisphosphonate, DOTA-Bn-SCN-BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three-step reaction scheme. Gallium-68- and Sm-complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate-buffered saline (PBS) and human serum. Both the complexes showed high affinity for hydroxyapatite particles in in vitro binding study. In biodistribution studies carried out in normal Wistar rats, both the complexes exhibited rapid skeletal accumulation with almost no retention in any other major organ. The newly synthesized molecule DOTA-Bn-SCN-BP would therefore be a promising targeting ligand for the development of radiopharmaceuticals for both imaging skeletal metastases and palliation of pain arising out of it in patients with cancer when radiolabeled with Ga and Sm, respectively. A systematic comparative evaluation, however, showed that there was no significant improvement of skeletal accumulation of the Sm-DOTA-Bn-SCN-BP complex over Sm-DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid) as the later itself demonstrated optimal properties required for an agent for bone pain palliation.

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Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases

Cited by 51 publications

References 133 publications

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Chelating agents for radiolanthanides: Applications to imaging and therapy

Syntheses and evaluation of ⁶⁸Ga‐ and ¹⁵³Sm‐labeled DOTA‐conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases

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Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases

Cited by 51 publications

References 133 publications

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Chelating agents for radiolanthanides: Applications to imaging and therapy

Syntheses and evaluation of 68Ga‐ and 153Sm‐labeled DOTA‐conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases

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Syntheses and evaluation of ⁶⁸Ga‐ and ¹⁵³Sm‐labeled DOTA‐conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases