Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [18F]AmBF3-TATE
2020; Springer Science+Business Media; Volume: 10; Issue: 1 Linguagem: Inglês
10.1186/s13550-020-0611-9
ISSN2191-219X
AutoresJoseph Lau, Jinhe Pan, Étienne Rousseau, Carlos Uribe, Sudhakara Reddy Seelam, Brent W. Sutherland, David M. Perrin, Kuo‐Shyan Lin, François Bénard,
Tópico(s)Radiopharmaceutical Chemistry and Applications
ResumoAbstract Introduction [ 18 F]AmBF 3 -TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [ 18 F]AmBF 3 -TATE were assessed with good laboratory practice (GLP) standards. Methods ICR mice were intravenously administered 0.8–2.0 MBq of [ 18 F]AmBF 3 -TATE, with one group pre-injected with 100 μg of [ 19 F]AmBF 3 -TATE 30 min before radiopharmaceutical administration to assess uptake specificity. The mice were euthanized at 0.5, 1, 2, or 4 h post-injection (p.i.). Blood and tissues were collected, weighed, and counted on a gamma counter to determine percentage injected dose per gram (%ID/g). Dosimetry was calculated based on biodistribution data using the mouse and human phantoms included in OLINDA. Acute toxicity was assessed in Sprague-Dawley rats at the dose of 0.742 mg/kg [ 19 F]AmBF 3 -TATE, with a 14-day observation/recovery period. Blood chemistry parameters, gross, and histopathology were evaluated. Body weight change and food consumption were monitored. The production of [ 18 F]AmBF 3 -TATE was automated on a Trasis AllinOne synthesis module. Results [ 18 F]AmBF 3 -TATE was cleared through the renal and hepatobiliary pathway. At 1 h p.i., the pancreas (F, 15.7 ± 3.72 and M 14.3 ± 1.61 %ID/g), stomach (F, 15.3 ± 3.63 and M, 19.0 ± 3.49 %ID/g), and lungs (F, 9.26 ± 2.24 and M, 6.17 ± 6.04 %ID/g) were the organs with the highest specific uptake. Pre-injection with [ 19 F]AmBF 3 -TATE significantly reduced pancreatic uptake (F, 0.13 ± 0.03 and M, 0.18 ± 0.09 %ID/g) at 1 h p.i. For dosimetry extrapolated to the average adult human, the bladder (0.027–0.030 mGy/MBq), pancreas (0.018–0.028 mGy/MBq), and lungs (0.006–0.013 mGy/MBq) are expected to receive the highest doses. No test-item related effects were observed upon evaluation of clinical observations, body weights, food consumption, clinical pathology, gross pathology, and histopathology for acute toxicity. [ 18 F]AmBF 3 -TATE was produced at activity yields of 15.6 ± 4.59 GBq, average molar activity of 435 ± 162 GBq/μmol, and radiochemical purity of 98.0 ± 1.73% with the automated synthesizer. Conclusion [ 18 F]AmBF 3 -TATE binds specifically to SSTR2. At 1000× clinical dose, [ 19 F]AmBF 3 -TATE was well tolerated with no treatment-related adverse effects.
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