Research target: We conducted the research to determine the distribution of 131I-nimotuzumab through the indication of the radioactivity in tissues of nude mice bearing human head and neck cancer tumors.
Trang 1BIODISTRIBUTION OF MONOCLONAL ANTIBODY NIMOTUZUMAB
AND NECK CANCER
Nguyen Thi Kim Huong*; Ho Anh Son**; Nguyen Thi Thu*** Pham Huy Quyen*; Nguyen Linh Toan**
SUMMARY
Research target: We conducted the research to determine the distribution of 131 I-nimotuzumab through the indication of the radioactivity in tissues of nude mice bearing human head and neck
cancer tumors Subject and methods: The 131 I-nimotuzumab was injected into the mice’s veins
at the dose of 100 µCi per mouse, and radioactivity was counted at three time points: 24, 48, and 72 hours after the injection Results: The research results showed that all the tissues and organs manifested the radioactivity In tumor, the radioactivity count was higher than that of any other organs The highest indication was 48 hours after the injection, and then gradually declined Radioactivity of the tumor was 79,26% compared to blood count at 72 hours after the injection Conclusion: With blood normalize, distribution of 131 I-nimotuzumab in tumors is the highest compared with other tissues and organs of the nude mice
* Key words: Head and neck cancer; Monoclonal antibody nimotuzumab labeled 131 I; Nude mice
INTRODUCTION
Head and neck cancer is a disease
with high incidence in the world, as well
as in Vietnam, about 10% of annual cancer
patients diagnosed with head and neck
cancer among total number of cancer
patients [1] Head and neck cancer is
varied and complex, expressed in multiple
locations, offices, including throat cancer,
mouth floor, lowering the larynx and throat,
salivary glands, tongue, thyroid , causing
the rear significant effects on health, the
patient lives if not diagnosed early and
treated promptly Head and neck cancer
has higher expression amount of EGFR
(EGFR: Epidermal Growth Factor Receptor)
in an unusual way, is one of the important pathogenetic factors of growth, invasion excessive encroachment cancer cells in multiple parts of the body [4] Previous studies have confirmed that blocking EGFR will inactivate or prevent the growth and metastasis of cancer cells, allowing the treatment to be effective One of the products targeted for treatment purposes
is 131I-nimotuzumab To evaluation effect
of 131I-nimotuzumab on head and neck cancer, in this study, we measured the distribution of 131I-nimotuzumab in the tissues of nude mice bearing human head
and neck cancer
* Institute of Nuclear Research
** Vietnam Military Medical University
*** Haiphong Pharmaco-Medical University
Corresponding author: Ho Anh Son (hoanhsonhp@gmail.com)
Trang 2SUBJECTS AND METHODS
1 Materials, chemicals
- Nimotuzumab monoclonal antibodies
labeled with 131I radioisotope, produced at
the Institute of Nuclear Research, radioactive
concentrations 100 mCi/mL
- Gamma counting camera
2 Research subjects
BALB/c immune deficiency mice without
T lymphocytes (nude mice, Foxn1nu)
imported from Charlie - River Company
(USA) They were kept in clean rooms,
and filtered air with positive pressure
Room temperature is maintained at 25 ±
20C and humidity of 55 ± 5%, the light is
automatically switched control at 7h00, off
at 19h00 Food (Zeigler, USA) and sterilized
water were ad libitum Each mouse cage
is put on a track system with independent
ventilation and membrane filtration ensures
the good isolation with pathogens
Mice transplanted larynx cancer cells
Hep 2 (106 cells/mouse), after tumor reached
diameter of about 10 mm, then each animal
was injected 100 µL 131I-nimotuzumab
(100 µCi each) and randomly divided into
3 groups:
+ Group 1 (n = 6): Radiation measurements
24 hours after injection
+ Group 2 (n = 6): Radioactivity measured
48 hours after injection
+ Group 3 (n = 6): Radioactivity measured
72 hours after injection
3 Research method
- Mice took lugol 1%, 1 drop/head, 24 hours
before injecting 131I-nimotuzumab complex
to block the thyroid gland, and then, daily ingested water mix with lugol (1 drop of lugol/5 mL water)
- 131I-nimotuzumab (100 Ci) was injected into mouse tail vein [2] Then, animals were deeply anesthetized and internal organs like liver, spleen, kidneys, heart, blood, muscle, intestine, lung, tumor and thyroid gland were removed to weigh and measure radiation in order to calculate the distribution for each tissue
RESULTS
1 Distribution of 131 I-nimotuzumab
in tissues of the mice
in tissues of mice after 24, 48 and 72 hours (counts/mg)
n = 18 ORGANS
AVERAGE RADIATION COUNTS
(10s)
Results of biological distribution in mice showed that 131I-nimotuzumab radioactive compound distributed the highest in the blood at all the times and tend to decrease
at the time 48 and 72 hours
Trang 3200.00
400.00
600.00
800.00
1000.00
1200.00
Blood Tumor Muscle Heart Lung Kidney Liver Bowel Thyroid Spleen
ave24g ave48g ave72g Activation of beta rays in tissues (count x 10 3 /mg/10sec)
The count in tumor tissue was the highest at 48 hours and equivalent compared with lung Other organ counts were lower than these two Radiation activity in other tissue was lower than those in tumor and lung
2 Comparing 131 I-nimotuzumab distribution in tissues compared to blood
Table 2: Radiation counts of tissues compared with blood
Biodistribution of 131I-nimotuzumab was the highest in blood at all time points and gradually reduced by the time
Ave 24g Ave 48g Ave 72g
Trang 420%
40%
60%
80%
100%
72g 48g 24g Counting ratios of tissues compared with the blood
Figure 2: Percentage of organs compared with the blood of nude mice
At the time 48 and 72 hours, normalize by blood counts, the radial activity of tumor
was the highest compared to other tissues
DISCUSSION
The distribution of radioactivity on the
tissues, including human head and neck
cancer tumors in nude mice showed that
it was expressed in all examined tissues,
and the ratios were different among
tissues, especially highest in the blood
(1114.42 μCi/g) and lowest in muscle
(95.94 μCi/g) at 24 hours after injection,
and then the radioactivity tends to decrease
at 48 hours and 72 hours after injection
After injection of 131I-nimotuzumab, antibody
molecules were concentrated in the blood
and had the highest ratio, then they will
move to the target tissue and attached to
its EGFR, so radioactivity decreased due
to degredation and elimination
On the contrary, in tumor, radioactive
count of 131I-nimotuzumab increased
gradually in 48 hours and it was higher
than other tissues which expressed high levels of EGFR in tumors, as other studies had demonstrated [4, 5], is the destination for the 131I-nimotuzumab attaches to and focus there, making the radiation increase
in tumor
High degree of EGFR expression in cancer cells is believed to be associated with increased levels of malignant progression as fast, easy-invasive and prone to relapse, but at the same time it is
a favorable factor for therapy destination and treatment are much better prospects
of therapeutic monoclonal antibodies used
in combination with radiation and anti-cancer
chemicals [3]
CONCLUSION
131I-nimotuzumab is showed in tissues after intravenous injection 24 hours and counting radioactive ratios in tissues were
Trang 5not equal, the highest expression levels in
time 48 hours after injection and then
decreased gradually Distribution of
131I-nimotuzumab in tumors compared with
blood was the highest in compare to other
tissues at 48 hours At 72 hours, it reached
79.26% against in blood
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