| Title |
177Lu-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment
|
|---|---|
| Published in |
EJNMMI Research, January 2016
|
| DOI | 10.1186/s13550-016-0161-3 |
| Pubmed ID | |
| Authors |
Ralf Bergmann, Marian Meckel, Vojtěch Kubíček, Jens Pietzsch, Jörg Steinbach, Petr Hermann, Frank Rösch |
| Abstract |
Metastatic bone lesion is a common syndrome of many cancer diseases in an advanced state. The major symptom is severe pain, spinal cord compression, and pathological fracture, associated with an obvious morbidity. 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. Agents utilizing beta-emitting radionuclides in routine clinical praxis are, for example, [(89)Sr]SrCl2 and [(153)Sm]Sm-EDTMP. No-carrier-added (n.c.a.) (177)Lu is remarkably suitable for an application in this scope. Five 1,4,7,10-tetraazacyclododecane N,N',N'',N''-tetra-acetic acid (DOTA)- and DO2A-based bisphosphonates, including monomeric and dimeric structures and one 1,4,7-triazacyclononane-1,4-diacetic acid (NO2A) derivative, were synthesized and labelled with n.c.a. (177)Lu. Radio-TLC and high-performance liquid chromatography (HPLC) methods were successfully established for determining radiochemical yields and for quality control. Their binding to hydroxyapatite was measured in vitro. Ex vivo biodistribution experiments and dynamic in vivo single photon computed tomography (SPECT)/CT measurements were performed in healthy rats for 5 min and 1 h periods. Data on %ID/g or standard uptake value (SUV) for femur, blood, and soft-tissue organs were analyzed and compared with [(177)Lu]citrate. Radiolabelling yields for [(177)Lu]Lu-DOTA and [(177)Lu]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 (177)Lu-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. (177)Lu-bisphosphonate dimers showed a slightly higher bone accumulation (SUVfemur = 4.48 ± 0.38 for [(177)Lu]Lu-DO2A(P(BP))2; SUVfemur = 5.41 ± 0.46 for [(177)Lu]Lu-DOTA(M(BP))2) but a slower blood clearance (SUVblood = 1.25 ± 0.09 for [(177)Lu]Lu-DO2A(P(BP))2; SUVblood = 1.43 ± 0.32 for [(177)Lu]Lu-DOTA(M(BP))2). 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 51 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 12% |
| Unspecified | 5 | 10% |
| Student > Ph. D. Student | 5 | 10% |
| Professor | 5 | 10% |
| Student > Bachelor | 4 | 8% |
| Other | 14 | 27% |
| Unknown | 12 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 14 | 27% |
| Medicine and Dentistry | 9 | 18% |
| Unspecified | 5 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 8% |
| Biochemistry, Genetics and Molecular Biology | 3 | 6% |
| Other | 4 | 8% |
| Unknown | 12 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 January 2016.
All research outputs
#20,302,535
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Outputs from EJNMMI Research
#386
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#329,785
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Outputs of similar age from EJNMMI Research
#8
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