Application of radioisotope tracer technology in the clinical research of biological drugs
10.3760/cma.j.cn114015-20210715-00792
- VernacularTitle:放射性同位素示踪技术在生物药临床研究中的应用
- Author:
Mingru ZHANG
1
;
Guoquan LI
;
Likun DING
;
Di ZHANG
;
Jiajun YE
;
Guiyu LI
;
Weidong YANG
;
Aidong WEN
;
Jing WANG
Author Information
1. 空军军医大学第一附属医院核医学科，西安 710032
- Publication Type:Journal Article
- Keywords:
Radioisotopes;
Biological products;
Pharmacokinetics;
Biodistribution;
Targeting
- From:
Adverse Drug Reactions Journal
2021;23(10):508-516
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the application value of radioisotope tracer technology in clinical research of biological drugs.Methods:The pharmacokinetic properties of mepuzumab in healthy volunteers were evaluated by measuring the radioactive concentrations of iodine in blood and urine samples of 3 healthy volunteers at different time points within 14 days after intravenous infusion of 131I-labeled international class I new drug mepuzumab (Trial 1). Positron emission computed tomography (PET/CT) was performed on 6 healthy volunteers after intravenous injection of 68Ga-labeled nucleic acid aptamer Sgc8, and the standard uptake values of 68Ga-Sgc8 in different organs were measured to evaluate its biodistribution in healthy humans (Trial 2). Nine patients with suspected neuroendocrine tumors underwent single photon emission and X-ray computed tomography (SPECT/CT) 4 hours after intravenous injection of 99mTc-labeled octreotide to determine the radioactive uptake level in the regions of interest; the affinity and targeting of 99mTc-labeled octreotide to somatostatin receptor subtype 2 (SSTR2) were evaluated in combination with the immunohistochemical staining results of SSTR2 in patients′ biopsy tissues (Trial 3). Results:The 3 healthy volunteers included in Trial 1 were male, aged 28, 45, and 25 years respectively; the injection doses of 131I-labeled mepuzumab were 21.0, 25.9, and 17.6 mg, and the injection doses of radioactivity were 364, 420, and 304 MBq, respectively. Among the 6 healthy volunteers included in Trial 2, 3 were male and 3 were female, with an age of (46±11) years, ranging from 35 to 63 years. The dose of radioactivity injected was (80±7) MBq, ranging from 69 to 87 MBq. Among the 9 patients included in Trial 3, 5 were male and 4 were female, with an age of (54±10) years, ranging from 39 to 69 years. The dose of radioactivity injected was (777±74) MBq, ranging from 740 to 925 MBq. After intravenous infusion of 131I-labeled mepuzumab, the blood radioactivity concentration reached the peak 1.5 hours later. 131I-labeled mepuzumab mainly bound to blood cells, and its whole-blood clearance half-life was 420 hours. The urine radioactivity concentration reached the peak 16-24 hours after administration and then gradually decreased after 24 hours of administration. After intravenous injection of 68Ga-labeled Sgc8, the organs with strong to weak radioactive signals were bladder, kidney, heart, uterus, liver, spleen, gallbladder, large intestine and lung. Within 3 hours after drug administration, the clearance rate was fastest in heart, followed by uterus, kidney, and liver; the clearance rate was slower in spleen and gallbladder and were slowest in large intestine and lung. All of the 9 patients had abnormal radioactivity accumulation 4 hours after intravenous injection of 99mTc-labeled octreotide and the immunohistochemical staining results of biopsy tissues showed strong positive expression of SSTR2, indicating that 99mTc-labeled octreotide had good affinity and targeting to SSTR2. The safety evaluation showed that in Trail 1, one subject developed iodine-related hyperthyroidism one month after intravenously infusion of 131I-labeled mepuzumab, which returned to normal after 8 months of continuous monitoring without intervention. No adverse reactions occurred in other subjects. Conclusions:Radioisotope tracer technology can noninvasively, dynamically, and visually evaluate the pharmacokinetics, biological distribution, and targeting of biological drugs in human body. It has good safety and great application value in the clinical evaluation of biological drugs.
