| Title |
99mTc-labelled S-HYNIC certolizumab pegol in rheumatoid arthritis and spondyloarthritis patients: a biodistribution and dosimetry study
|
|---|---|
| Published in |
EJNMMI Research, December 2016
|
| DOI | 10.1186/s13550-016-0245-0 |
| Pubmed ID | |
| Authors |
Bieke Lambert, Philippe Carron, Yves D’Asseler, Klaus Bacher, Filip Van den Bosch, Dirk Elewaut, Gust Verbruggen, Rudi Beyaert, Caroline Dumolyn, Filip De Vos |
| Abstract |
Biologicals directed against tumour necrosis factor (TNF) have proven their efficacy in the treatment of spondyloarthritis and rheumatoid arthritis. We present a radiolabelling method for certolizumab pegol (CZP), a commercially available humanized Fab'-fragment directed against TNF. A biodistribution and dosimetry study was conducted. Tc-S-HYNIC CZP was synthesized. The in vitro TNF neutralizing activity was tested by exposing L929s-cells to various concentrations 99mTc-S-HYNIC CZP and measuring TNF-induced cytotoxicity. For biodistribution and dosimetry, WB images and blood and urine sampling were performed up to 24 h pi. Cumulative activities were estimated using mono-exponential fitting, and organ doses were estimated using OLINDA/EXM. The effective dose was calculated using the International Commission on Radiological Protection 103 recommendations. The uptake of the tracer in the peripheral joints was assessed visually and semiquantitatively. In vitro tests showed blocking of TNF cytotoxicity by the (99m)Tc-S-HYNIC CZP formulation comparable to the effect obtained with the unlabelled CZP with or without the HYNIC linker. We analysed eight patients with rheumatoid arthritis or spondyloarthritis. The highest mean absorbed organ doses were recorded for kidneys, spleen, and liver: 56 (SD 7), 34 (SD 6), and 33 (SD 7) μGy/MBq. The effective dose was 6.1 (SD 0.9) mSv for a mean injected activity of 690 (SD 35) MBq. The urinary excretion was 15.1% (SD 8.1) of the IA at 22.5 h. Blood analysis yielded a distribution half-life of 1.2 h (SD 1.5) and an elimination half-life of 26.9 h (SD 2.7). Visual analysis of the scans revealed marked tracer accumulation in the clinically affected peripheral joints. In addition, there was a statistically significant higher uptake of the tracer in the swollen joints (median uptake ratio compared to background of 3.3 in rheumatoid arthritis and 2.4 in peripheral spondyloarthritis) compared to clinically negative joints (respectively 1.3 and 1.6). We present a radiolabelling technique for CZP, a Fab'-fragment directed against TNF and currently used as a therapeutic agent in rheumatology. An effective dose of 6.1 mSv (SD 0.9) was estimated. We confirmed the uptake of this new radiopharmaceutical in clinically affected peripheral joints. |
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 % |
|---|---|---|
| Belgium | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 19% |
| Researcher | 5 | 16% |
| Student > Bachelor | 3 | 10% |
| Student > Master | 3 | 10% |
| Professor | 3 | 10% |
| Other | 3 | 10% |
| Unknown | 8 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 29% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 19% |
| Agricultural and Biological Sciences | 3 | 10% |
| Biochemistry, Genetics and Molecular Biology | 1 | 3% |
| Sports and Recreations | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 8 | 26% |
Attention Score in Context
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#20,397,576
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Outputs from EJNMMI Research
#391
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#353,822
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Outputs of similar age from EJNMMI Research
#10
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