Evaluation of bone-seeking novel radiotracer 68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

Passah, Averilicia; Tripathi, Madhavi; Ballal, Sanjana; Yadav, Madhav P.; Kumar, Rajeev; Roesch, Frank; Meckel, Marian; Chakraborty, Partha Sarathi; Bal, Chandrasekhar

doi:10.1007/s00259-016-3469-3

Cited by 24 publications

(25 citation statements)

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“…These positive results were also confirmed in a prospective patient study by Passah et al comparing [ 68 Ga]Ga-NO2AP BP , [ 18 F]NaF, and [ 99m Tc]Tc-MDP in female breast cancer patients with osseous metastases [29]. Within this study, the NOTA-based bisphosphonate was able to underline its high diagnostic efficiency.…”

Section: Design and Development Of Radiolabeled Bisphosphonatessupporting

confidence: 81%

“…Comparison of [ 99m Tc]Tc-MDP, [ 68 Ga]Ga-NO2AP BP , and [ 18 F]NaF in a breast cancer patient with bone metastases [29]. [ 99m Tc]Tc-MDP demonstrates abnormal uptake only in the skull, cervical vertebra, sternum, two ribs on the right side, and pelvis, while both [ 68 Ga]Ga-NO2AP BP and [ 18 F]NaF distinctly show more lesions in the skull, cervical, thoracic, lumbar and sacral vertebrae, pelvis, and both femorae.…”

Section: Figurementioning

confidence: 99%

“…[ 99m Tc]Tc-MDP demonstrates abnormal uptake only in the skull, cervical vertebra, sternum, two ribs on the right side, and pelvis, while both [ 68 Ga]Ga-NO2AP BP and [ 18 F]NaF distinctly show more lesions in the skull, cervical, thoracic, lumbar and sacral vertebrae, pelvis, and both femorae. [ 68 Ga]Ga-NO2AP BP and [ 18 F]NaF are equivalent regarding the number of detected lesions and far superior than [ 99m Tc]Tc-MDP [29]. …”

Section: Figurementioning

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: Design and Development Of Radiolabeled Bisphosphonatessupporting

confidence: 81%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

et al. 2017

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“…Alendronic acid is used in the clinic to treat osteoporosis, and it accumulates in areas with high bone turnover [20]. TCO-modified alendronic acid has been used to screen radiolabelled tetrazines for in vivo pretargeting in healthy mice [21–23] [20, 24, 25]. The possibility to screen in healthy animals is advantageous for applications in higher order species because a disease model is not needed.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging

et al. 2019

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Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans -cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111 In-labelled Tz to image TCO-functionalized antibodies in tumour-bearing mice. Since then, the IEDDA has been used extensively in pretargeted nuclear imaging and radiotherapy; however, these studies have only been performed in mice. Herein, we report the 44 Sc labelling of a Tz and evaluate it in pretargeted imaging in Wistar rats. Results 44 Sc was obtained from an in house 44 Ti/ 44 Sc generator. A 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-functionalized tetrazine was radiolabelled with 44 Sc resulting in radiochemical yields of 85–95%, a radiochemical purity > 99% at an apparent molar activity of 1 GBq/mmol. The 44 Sc-labelled Tz maintained stability in solution for up to 24 h. A TCO-functionalized bisphosphonate, which accumulates in skeletal tissue, was used as a targeting vector to evaluate the 44 Sc-labelled Tz. Biodistribution data of the 44 Sc-labelled Tz showed specific uptake (0.9 ± 0.3% ID/g) in the bones (humerus and femur) of rats pre-treated with the TCO-functionalized bisphosphonate. This uptake was not present in rats not receiving pre-treatment (< 0.03% ID/g). Conclusions We have prepared a 44 Sc-labelled Tz and used it in pretargeted PET imaging with rats treated with TCO-functionalized bisphosponates. This allowed for the evaluation of the IEDDA reaction in animals larger than a typical mouse. Non-target accumulation was low, and there was a 30-fold higher bone uptake in the pre-treated rats compared to the non-treated controls. Given its convenient half-life and the ability to perform positron emission tomography with a previously studied DOTA-functionalized Tz, scandium-44 ( t 1/2 = 3.97 h) proved to be a suitable radioisotope for this study. Electronic supplementary material The online version of this article (10.1186/s13550-019-0520-y) contains supplementary material, which is available to authorized users.

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“…It was envisaged that the affinity of the radiotracer for bone and particularly for metastatic skeletal lesion sites could be enhanced by coupling bisphosphonate with a suitable bifunctional chelator (BFC) for complexing 68 Ga, such that the bisphosphonate moiety is free for binding with HA on the bone surface. In recent years, the syntheses and evaluation of a number of 68 Ga‐complexes of BFC‐bisphosphonate conjugates using DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) and NOTA (1,4,7‐triazacyclododecane‐1,4,7‐triacetic acid) derivatives have been reported . This concept of using BFC‐bisphosphonate conjugate for efficient targeting of skeletal metastases has also been successfully used for the palliative care of pain arising from skeletal metastases with therapeutic radionuclides …”

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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Evaluation of bone-seeking novel radiotracer 68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

Cited by 24 publications

References 19 publications

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging

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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Evaluation of bone-seeking novel radiotracer 68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

Cited by 24 publications

References 19 publications

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging

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