Impression: Acute Radiation Disease include development of radiation toxicity after Reactive Oxygen Species, Reactive Nitrogen Species, Hydrolytic enzyme leakage from lysosomes and Golgi apparatus , radiation cell necrosis, regional and general inflammation, vasculitis, acute autoimmune reactions development. Specific Therapeutic Monoclonal Antibodies can play role of Anti Radiation Antidote and inhibit hydrolytic enzyme activation and toxicity, prevent inflammation and autoimmune reactions. Specific Therapeutic Monoclonal Antibodies can protect mammals against high doses of radiation and biological sequela after radiation.

1. Anti radiation Antidote:
Inhibition and neutralization of
Radiation Toxicity with
Therapeutic Monoclonal
Antibodies .
DMITRI POPOV. PHD, RADIOBIOLOGY.
MD (RUSSIA)
ADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC. CANADA.
INTERVACCINE@GMAIL.COM

2. DOI: 10.13140/RG.2.1.1476.6805
Anti radiation Antidote:
Inhibition and neutralization of
Radiation Toxicity with
Therapeutic Monoclonal
Antibodies .

3. Anti radiation Therapeutic
Monoclonal Antibodies.
 Antibodies become a clinically important
drug class: more than 25 antibodies are approved for
human therapy and more than 300 antibodies are currently in clinical
development worldwide for a wide range of diseases,
including autoimmunity and inflammation, protection against radiation
cancer , organ transplantation, cerebrovascular disease,
cardiovascular disease, infectious diseases and ophthalmological
diseases.
http://www.nature.com/nri/journal/v10/n5/abs/nri2761.html
https://www.google.ca/webhp?sourceid=chrome-
instant&ion=1&espv=2&ie=UTF-8#q=radiation%20toxins
http://pubmedcentralcanada.ca/pmcc/articles/PMC3929455/

4. Anti radiation Therapeutic
Monoclonal Antibodies.
 Cytokine and growth factor blockade.
 The first therapeutic antibody for the treatment of inflammatory
 diseases was infliximab (Remicade; Centocor/Merck), in
 1998, for the treatment of Crohn’s disease.
 Mechanisms of action of therapeutic antibodies. Five non-overlapping
 mechanisms of action are depicted. Examples of therapeutic antibodies are listed for
 each mechanism of action depicted. Ligand blockade with full length IgG
therapeutic
 antibodies (for example, infliximab, adalimumab or golimumab), antibody fragments
 (for example, certolizumab pegol) or receptor immunoadhesins (for example,
etanercept
 and those indicated with ‡) can prevent ligands from activating their cognate
receptors.
 http://www.nature.com/nri/journal/v10/n5/abs/nri2761.html

5. Anti inflammatory therapeutic
antibodies. Mechanisms of action.
 Binding of ligands (for example, interleukin-6 (IL-6)) to receptors (for
example, IL-6R) can also be blocked by antibodies directed to their
cognate receptors and inhibit receptor activation or function. Binding
of cell surface receptors by antibodies can also result in
their internalization and downregulation to limit cell surface
receptors that can be activated by the ligand.
 Binding of cell surface receptors by antibodies (for example, αL integrin
by efalizumab) or binding of a ligand (for example, free serum IgE
 by omalizumab) can indirectly also result in downregulation of cell
surface receptors available for cellular activation. Binding of cell
surface receptors can result in depletion of antigen-bearing cells
through complement-mediated lysis and opsonization, as well
as Fc receptor for IgG (FcγR)-mediated clearance.
http://www.nature.com/nri/journal/v10/n5/abs/nri2761.html

6. Anti inflammatory therapeutic
antibodies. Mechanisms of action.
 Therapeutic antibodies can also induce active signals that alter cellular fates. Binding
of the T cell receptor (TCR)–CD3
 complex by teplizumab can induce TCR-mediated signals and alter T cell functions
and differentiation. MAC, membrane attack complex; TNF, tumour necrosis factor;
TNFRI; TNF receptor I. *Antibodies with several mechanisms of action.
 Receptor blockade and receptor modulation. in addition to ligand blockade,
therapeutic antibodies can also block ligand–receptor interactions by targeting the
 receptor . These include antibodies that target the il-6 receptor (tocilizumab
(Actemra/RoActemra; Chugai/Roche)), αl integrin (also known as CD11a
 and lFA1) (efalizumab (Raptiva/Xanelim; Genentech/Roche/Merck–Serono)), the α4
subunit of α4β1 and α4β7 integrins (natalizumab (Tysabri; Biogen idec/Elan)) and
α4β7 integrin (vedolizumab (MlN2; Millennium Pharmaceuticals/Takeda)). Targeting
of receptors adds a
 secondary level of mechanistic activity as a subset of these therapeutic antibodies
not only blocks ligand binding butalso downregulates the cell surface expression of
the targeted receptors.
 http://www.nature.com/nri/journal/v10/n5/abs/nri2761.html

7. Anti Radiation Therapeutic Monoclonal
Antibodies.
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005344/
 Acute Radiation Disease include Five Syndromes:
 Acute Radiation Cerebrovascular Syndrome.
 Acute Radiation Cardiovascular Syndrome.
 Acute Radiation Gastro Intestinal Syndrome.
 Acute Radiation Hematopoietic Syndrome.
 Acute Radiation Immunologic Syndrome, which include Acute
Radiation Systemic Inflammatory Response Syndrome, and Acute
Radiation Systemic Autoimmune Syndrome .
 http://www.slideshare.net/dlpopov/acute-radiation-
diseasedefinition

8. Anti radiation Therapeutic
Monoclonal Antibodies.
 Systemic inflammatory response syndrome (SIRS) is an inflammatory
state affecting the whole body, frequently a response of the
immune system to radiation or infection.
 It is related to sepsis or high doses of Radiation, a condition in which
individuals meet criteria for SIRS and have a known infection or
irradiated with high doses of Radiation such as gamma radiation,
heavy ion radiation, neutron radiation, proton radiation, X ray
radiation. SIRS is a sysytemic condition related to systemic
inflammation, organ dysfunction, and organ failure. It is a subset
of cytokine storm, in which there is abnormal regulation of various
cytokines.
SIRS is also closely related to sepsis, in which patients satisfy criteria
for SIRS and have a suspected or proven infection.

9. Monoclonal Antibodies.
 SIRS is also closely related to high doses of radiation and cell necrosis
induced by irradiation , in which patients satisfy criteria for SIRS and
have a suspected or proven post radiation status.
 https://www.google.ca/webhp?sourceid=chrome-
instant&ion=1&espv=2&ie=UTF-8#q=radiation%20toxins

10. Monoclonal Antibodies.
 Radiation Toxic Multiple organ dysfunction syndrome (RT MODS),
previously known as Radiation Toxic multiple organ failure (RT MOF)
or Radiation Toxic multisystem organ failure (RT MSOF), is
altered organ function in an irradiated patients.
 https://www.google.ca/webhp?sourceid=chrome-
instant&ion=1&espv=2&ie=UTF-8#q=radiation%20toxins

11. Monoclonal Antibodies and Acute
Radiation Cytokine Storm.
 A cytokine storm, also known as cytokine
cascade and hypercytokinemia, is a potentially fatal immune
reaction consisting of a positive feedback
loop between cytokines and white blood cells, with highly elevated
levels of various cytokines.
 Local and systemic responses are initiated by tissue damage after
irradiation by Reactive Oxygen Species, Reactive Nitrogen Species,
Hydrolytic Enzymes and secondary by cytokine activation.
Respiratory failure is common in the first 72 hours after the original
insult. Subsequently, one might see liver failure ( 1–7
days), gastrointestinal bleeding (hours–days) and kidney failure (11–
17 days)

12. Monoclonal Antibodies.
 Acute Radiation Vasculitis.
 http://www.slideshare.net/dlpopov/acuteradiation-disease-acute-
radiation-vasculitis
 Acute Radiation Angioedema.
 https://www.google.ca/webhp?sourceid=chrome-
instant&ion=1&espv=2&ie=UTF-8#q=radiation+angioedema
 http://www.ncbi.nlm.nih.gov/books/NBK209/
 https://books.google.ca/books?id=40Z9CAAAQBAJ&pg=RA6-
PA35&lpg=RA6-
PA35&dq=radiation+angioedema&source=bl&ots=SlzS6mbrMR&sig=Yw
hd964EFhJy3Rg5CJtZ1uRr2Qc&hl=en&sa=X&ved=0CEEQ6AEwBmoVCh
MIiJaQ_c69yAIVCaUeCh2ZZAkp#v=onepage&q=radiation%20angioed
ema&f=false

13. Therapeutic Monoclonal Antibodies and Radiation
Angioedema.
 Angioedema with swelling of larynx is a serious allergic reaction and can be life-
threatening. It can occur after exposure to various triggers and usually it is very
difficult for the patient and the doctor to find the trigger and maintain complete
remission. In idiopathic recurring angioedema presenting with frequent attacks,
prophylaxis with H1 antihistamines recommended. However, not all patients
respond to antihistamines. Omalizumab is an anti-immunoglobulin (Ig)-E-Ig-G
antibody approved for the treatment of asthma and also effective treatment in
chronic spontaneous urticaria. We report a 47-year-old male patient with severe
idiopathic angioedema controlled by corticosteroid and proggressed after
discontining of corticosteroid because of its side effects. Omalizumab at a dose
of 300 mg every 4 weeks was administrated and omalizumab provided a rapid
clinical response after first injection. During the 4 months of omalizumab therapy,
he had no further attacks and any other treatment needs. After 3 months of
stopping omalizumab therapy, during the 4-week period he had two mild lip
swelling in his lips that resolved with antihistamines.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005344/
 Asia Pac Allergy. 2014 Apr; 4(2): 129–130. Ayse Bilge Ozturk et al.
 Published online 2014 Apr 29. doi: 10.5415/apallergy.2014.4.2.129

14. Monoclonal Antibodies.
 Acute Radiation Hepatitis.
 http://www.ajronline.org/doi/abs/10.2214/ajr.117.1.73
 http://www.ncbi.nlm.nih.gov/pubmed/547358
 http://onlinelibrary.wiley.com/doi/10.1002/hep.510260117/pdf

15. Monoclonal Antibodies.
 Acute Radiation Pneumonitis.
 Radiation pneumonitis is the acute manifestation of radiation-
induced lung disease (RILD) and is relatively common following
radiotherapy for chest wall or intrathoracic malignancies. This article
does not deal with changes seen in the the late phase.
 Radiation pneumonitis - Radiopaedia.org
 radiopaedia.org/articles/radiation-pneumonitis
 http://www.cancer.ca/en/cancer-information/diagnosis-and-
treatment/radiation-therapy/side-effects-of-radiation-
therapy/radiation-to-the-chest/radiation-pneumonitis/?region=on
 http://jjco.oxfordjournals.org/content/29/4/192.full

16. Monoclonal Antibodies and bone marrow
protection and resistance against radiation.
 Acute Radiation Hematopoietic Syndrome.

17. Monoclonal Antibodies.
 Acute Radiation Immunologic Syndrome: Sub Type - Acute
Radiation Autoimmune processes.
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935336/
 http://www.ncbi.nlm.nih.gov/pubmed/8133066
 http://press.endocrine.org/doi/full/10.1210/jc.2005-0286
 https://flutrackers.com/forum/forum/welcome-to-the-scientific-
library/radiation-exposure-effects-on-humans-food-chain-
environment/117546-radiation-and-autoimmune-disease

18. Monoclonal Antibodies.
 Scientists at the Stanford University School of Medicine found that
"Ionizing radiation can functionally alter the immune system and
break self-tolerance"(a technical term for when radiation breaks
down the normal ability to fight off disease). The study is published in
the Journal of Immunology. The researchers irradiated the thymus
and the peripheral lymphoid organs/tissues in mice to induce the
autoimmune response. Total lymphoid irradiation on mice caused
various organ-specific autoimmune diseases, such as gastritis,
thyroiditis, and orchitis, depending on the radiation dosages, the
extent of lymphoid irradiation, and the genetic background of the
mouse strains. They concluded, "these results indicate that high
dose, fractionated ionizing radiation on the lymphoid organs/tissues
can cause autoimmune disease by affecting the T cell immune
system."

19. Monoclonal Antibodies.
 http://www.ncf-
net.org/radiation/LoganovskyLowDoseIonizingRadiationBrain.pdf
 Radiation exposure has multiple effects on the brain, behavior, and
cognitive functions. These changes depend largely on the dose
received. It is well known that ionizing radiation influences CNS
functions and behavior both as a result of direct effects on the
nervous system and indirectly through CNS reactivity to the radiation
damage of other systems (Kimeldorf & Hunt, 1965; Mickley, 1987)

20. Monoclonal Antibodies.
 According to the data of the State Register of Ukraine and Clinical
and Epidemiological Registry (Scientific Centre for Radiation
Medicine, Kiev) there is an increased level of cerebrovascular
disorders in liquidators and evacuees. Exposure to small doses of
ionizing radiation is a significant risk factor of accelerating aging.
Thyroid exposure by 300 mGy and more is a significant risk factor for
vascular and cerebrovascular disorders. Thyroid exposure by 2 Gy
and more is a significant risk factor for mental disorders, vascular
and cerebrovascular diseases, and peripheral nervous system
disorders. Exposure to doses of 250 mGy and more is a significant risk
factor for neuropsychiatric disorders and vascular disorders. There is
a dose–effect relationship for cerebrovascular disorders in liquidators
– military and civic personnel. http://www.ncf-
net.org/radiation/LoganovskyLowDoseIonizingRadiationBrain.pdf

21. Monoclonal Antibodies.
 Occupational exposure and neurotoxicity of Uranium and
transuranium elements: implementation at the Shelter Object of the
Chernobyl NPP .

22. Monoclonal Antibodies.
 The available data on neuropsychiatric effects of occupational exposure are
quite limited and contradictory. The most comprehensive related study was
conducted by Azizova (1999) in atomic industry workers exposed to chronic
occupational ionizing radiation, mainly external γ-irradiation. Vegetative-
vascular dystonia, predominantly hypothensive, asthenic syndrome, and
demyelinizating encephalomyelosis syndrome were the main neurological
clinical patterns. Their rate was in proportion to the radiation dose. Together with
hematological abnormalities (thrombocytopenia and leukocytopenia), these
were considered to be the neurological features of Chronic Radiation Sickness.
Demyelinizating encephalomyelosis was observed only at doses of 2–4 Sv and
more. Cerebrovascular pathology was the most common in the remote period
after irradiation. Radiation risk for cerebral atherosclerosis has been revealed;
however, no connection between the dose and stroke rate has been found.
 http://www.ncf-
net.org/radiation/LoganovskyLowDoseIonizingRadiationBrain.pdf

23. Specific Therapeutic Monoclonal Antibodies –
Anti radiation Antidote. .
 Impression:
 Acute Radiation Disease include development of radiation toxicity
after Reactive Oxygen Species, Reactive Nitrogen Species,
Hydrolytic enzyme leakage from lysosomes and Golgi apparatus ,
radiation cell necrosis, regional and general inflammation, vasculitis,
acute autoimmune reactions development.
 Specific Therapeutic Monoclonal Antibodies can play role of Anti
Radiation Antidote and inhibit hydrolytic enzyme activation and
toxicity, prevent inflammation and autoimmune reactions.
 Specific Therapeutic Monoclonal Antibodies can protect mammals
against high doses of radiation and biological sequela after
radiation.