Submitted By Marwa M. AL-A’qarbeh

O

OH

OH

18F

NN

NO2

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Hypoxia Cell/Hypoxia

Tissue

Hypoxia Cell/Hypoxia

Tissue

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HypoxiaHypoxia:: the reduction or lack of oxygen in

organs, tissues, or cells.

This decrease of oxygen tension can be due to a reduced supply in oxygen, As a result of anemia

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HypoxiaHypoxia

Hypoxia can be physiologic or pathologic such as in solid cancers , rheumatoid arthritis, atherosclerosis.

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HypoxicAnemicHypemicHistotoxicStagnant

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Hypoxic - occurs when the entire body doesn't

receive an appropriate amount of oxygen supply, and as a result, there is a low partial pressure of oxygen in the arterial blood

- Potential causes of Hypoxic hypoxia entail high altitude ascension, sleep apnea, inappropriate ventilation, or a heart mechanism failure

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is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are in result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue

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1.  HIF-1 induced changes in gene expression2. GLUT1 transporter expression3.  Hexokinase 2 expression4.  Phosphoglucose isomerase expression5.  6-Phosphofructo-2-kinase/fructose 2,6-

bisphosphatases expression6.  Fructose-1,6-bisphosphate aldolase expression7. Glyceraldehyde-3-phosphate dehydrogenase

expression8.  Phosphoglycerate kinase 1 expression9. Phosphoglycerate mutase expression10.  Enolase 1 expression11.  Pyruvate kinase expression12. Pyruvate dehydrogenase kinase expression13.  Lactate dehydrogenase expression

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Ionizing radiation + H2O [H2O+] + e- *OH + H+ + e-

*OH + DNA DNA* or DNAOH*

In the presence of oxygen

DNA* + O2 DNAOO*

In the absence of O2

DNA* + RSH DNA + RS*

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PET-Scan Techniques

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An acronym of Positron Emission

Tomography, PET is an analytical nuclear

medicine imaging technology, it uses positron

labeled molecules in very low mass amounts to

image and measure the function of biological

processes with minimal disturbance, using

radiolabeled molecules to image molecular

interactions of biological processes in vivo

(Phelps, 2000). 19

analytical nuclear medicine imaging technology,

a positron-labeled molecule is used in very low

mass amount to image and measure the function of

biological processes with minimal disturbance

(Phelps, 2000; Phelps et al., 1975).

Measuring without disturbing, the biological

process a fundamental and biologically important

aspect of PET tracer technique.20

first an input function taken from the plasma to represent

the delivery of the labeled probe.

Second the PET measure of the tissue concentration of the

labeled probe and its labeled reaction products in organs.

third a compartmental model often the assay models are

used to produce sufficient knowledge to allow a simpler,

qualitative approach to meet the needs of a clinical service

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(Phelps, 2000)

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3 – Dimensional (3D) PET.

PET/ CT scanner .

Time-of- Flight (TOF) PET.

Very –High- Resolution Preclinical PET.

Micro PET.

Whole - Body PET 24

Whole body PET (3D) from (Cherry, 2006)

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micro PET from (Phelps, 2000) 

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Studying of some biological process, (e.g. glucose metabolism)

drug metabolism and banding in human body, Blood flow,

metabolic of cardiac tissue, and process in brain (Laverman et al.,

2008; Phelps, 2000)

Dementia and Alzheimer's diseases

Cancer, by accurate diagnosis of primary and recurrent tumor,

accurate determination of tumor extent after diagnosis, and

Prediction and assessment of treatment response (Phelps, 2000).

Detection of asymptomatic disease (Phelps, 2000)

Imaging gene expression in vivo (Schlyer, 2004; Phelps, 2000)

Imaging of hypoxia tissue

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Nuclide Half-life Decay mode (%) E β+, max (keV)

11C 20.4 min β+ (99.8), EC (0.2) 960

13N 9.96 min β+ (100) 1190

15O 2.03 min β+ (99.9), EC (0.1) 172030P 2.5 min β+ (99.8), EC (0.2) 325018F 109.6 min β+ (97), EC (3) 635

75Br 98 min β+ (75.5), EC (24.5) 174076Br 16.1 h β+ (57), EC (43) 3900

120I 1.35 h β+ (64), EC (36) 410038K 7.6 min β+ (100) 2680

62Cu 9.7 min β+ (98), EC (2) 2930

64Cu 12.7 h β+ (18), β- (37), EC (45) 65568Ga 68.3 min β+ (90), EC (10) 190094Tc 52 min β+ (72), EC (28) 247082Rb 1.3 min β+ (96), EC (4) 335072As 26 h β+ (88), EC (12) 2515

38K 7.6 min β+ (100) 268086Y 14.7 h β+ (34), EC (66) 130029

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[18F]FDG2-[18F]fluoro-2-deoxy-D-

glucose

Glucose

metabolism

(Iodo et al.,

1979)

O

OH

HO OH

HOF

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31

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NN

HN

CF3O

FF

NO2

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[18F]EF52-(2-nitro-1[H]-imidazol-1-yl)-N-

(2,2,3,3,3-pentafluoropropyl)-aceamide

Tissue hypoxia

[18F]FAZA2-Fluoromethyl-5-(2-nitro-

imidazol-1-yl)-tetrahydro-furan-

3,4-diol

Hypoxia tissue

marker

(Kumar et al.,

1999)

O

OH

OH

18F

NN

NO2

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[18F]FETNIM4-[18F]fluoro-2,3-dihydroxy-1-(2-

nitroimidazol-1-yl)-butanol

Tissue hypoxia

OH

NN

N+

O

-O

OH

OH

18F29

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Ro-07-

0741

(FMISO)

1-Fluoro-3-(2-nitro-imidazol-

1-yl)-propan-2-ol)

Hypoxia

tissue marker

Called golden

hypoxia pet

marker

(Hodgkiss et

al.1998)

NN

NO2

18F

OH

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Purpose of

Reserch

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NN

NO2

18F

OH

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(FMISO)

Hodgkiss et al.1998)

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Expermantal work

Expermantal work

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Cold Synthesis

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Hot synthesis pathway “done by Dirk Loffler, at Tubingen university

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400 MHz 1H-NMR (CDCl3)

60 MHz 13C – NMR (CDCl3)

FT -HRMS

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Compound

%yield Calc. M. mass

Found M.mass (HR-MS)[M+1]+

a 84 302.0651 6303.065

b 91 316.0807 317.0817

c 81 330.0964 331.0964

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Compound

%yield Calc. M. mass

Found M.mass (HR-MS)[M+1]+

a 77 172.0596 173.0591

b 72 186.08257 187.08266

c 83 200.09094 201.09082

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Compound

%yield Calc. M. mass

Found M.mass (HR-MS)[M+1]+

a 89 278.08152 279.08147

b 92 292.10444 293.10426

c 83 306.12064 307.12012

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Thank you

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