**3.1 Sugar metabolism**

Cancerous cells proliferate rapidly and get more energy to fulfill physiological activities. Glucolysis is the preliminary energy driving metabolism. What would happen if the same metabolism used for imaging cell?

**105**

*Localization Mechanisms of Radiopharmaceuticals DOI: http://dx.doi.org/10.5772/intechopen.94099*

An analogous molecule of glucose but not sugar it has one oxygen atom less than glucose. Fluorine (F- 18), a cyclotron based radionuclide labeled with glucose analogous (deoxyglucose) through nucleophilic reaction with mannos triflate (precursor) [2]. **18F-FDG (fluorodeoxyglucose**) practice for clinical oncology since 1980s [46]. The fluorodeoxyglucose participate and transport inside cell by following the same pathway as glucose through glucose transporter; GLUT-1. This glucose transpoter GLUT-1 release in stress condition and a member of glucose regulating protein [45]. As said earlier deoxyglucose is a glucose analogous, so this analogous molecule metabolized by the same pathway as glucose and was trapped in place of glucose molecule and get phosphorylated (glycolysis) as shown in **Figure 12**. Glucose-6-phosphate further participate in glycolysis but FDG-6- phosphate cannot metabolized (not being the subsequent substrate) as glycolytic enzyme glucose-6-phosphate isomerase (hexokinase) has strict structural and geometric demands so fluorine substituted; 2-oxy-2-fluoro-D-glucose trapped and accumulate inside cell cytoplasm (metabolic trapping) [44]. Remember that glucose and FDG compete for the same transporter GLUT-1, so higher glucose level may lower the uptake of FDG. The enzyme hexokinase may convert back fluoro-6-phosphate to FDG but cancerous cell have very low amount of this enzyme so this trapped molecule (18FDG-6-PO4) aid in-vivo study of homeostatic system without disturbing their function. 18F-FDG is presently the most widely used PET tracer for imaging

non-invasive malignant tissues that highly metabolized glucose [45].

infection and sterile inflammation.

dosimetry and cell biodistribution [48].

**3.2 Iron metabolism**

*3.1.2 Sorbitol*

The 18F-fluorodeoxyglucose participate in imaging of osteomyelitis, spinal infections, endocarditis, infected joint prosthesis, diagnose FUO and diabetic foot infection. Limitation regarding 18F-FDG use that it cannot differentiate between

Another alcohol soluble sugar; **sorbitol**, act as a metabolic substrate for bacterial specific imaging. Gram negative bacterial strains (*Klebsiella pneumoniae*, *Escherichia coli*, Yersinia pestis, Enterobacter spp., etc.) show promising findings but limited detection in case of Gram-positive bacteria and mammalian cancer cells. Sorbitol was taken up by the bacterial surface membrane transporter, then phosphorylated and metabolized in the same manner as glucose. Initially 18F-FDG reduce to 18F-FDS (fluorodeoxysorbitol) as shown in **Figure 14** than transported to bacterial cell environment where analogous glucose metabolism begin next [47]. Interesting fact is that mammalian cells did not have transporter for this sugar [43]. Moreover, 18F-FDS act as promising agent in PET imaging for monitoring efficacy of antibacterial burden and proved to be safe for intravenous human use that determine radiation

For the development of new radiopharmaceuticals similarities with ferric ion (Fe+3) was very important as iron is a fundamental part of our body and many iron binding proteins likewise transferrin, lactoferrin and ferritin transport and store iron in-vivo. 67Ga++ ion produced at physiological pH its infection uptake is multifactorial since it shares similar chemical characteristic and biodistribution properties with ferric ion (Fe+3). When 67Ga- citrate administrated in blood plasma due to the increase cell permeability and blood flow about 90% activity exchange ligand

*3.1.1 Deoxyglucose*

## *3.1.1 Deoxyglucose*

*Medical Isotopes*

marrow imaging) [40].

metabolism and

• Sugar metabolism

• Iron metabolism

• Lipid metabolism

**3.1 Sugar metabolism**

• Amino acid metabolism

imaged accessory spleen tissues [45].

111In-oxine labeled leukocytes preferably practiced for the diagnosis and therapy of inflammatory bowel disease, osteomyelitis, abdominal infection, diabetic foot, vascular prosthesis, pelvic sepsis, lung infection, fever of unknown origin, neurological infection, and endocarditis etc. Furthermore, for the ex-vivo radio-labeling sterile conditions should be taken because there was a possible risk of cross con-

**99mTc- exametazime (HMPAO)** labeled with autologus leukocytes (predominantly neutrophils) follow the same pathway for infection and inflammation imaging as 111In-oxine labeled leukocytes. Neutrophil, an important part of our innate immune system moved towards acute infection foci and invade pathogens [45]. Labelling of leukocytes followed by intervenously administration of radiolabelled complex, due to inflammatory cytokines and chemokines; WBCs were attracted towards infection site. The 99mTc-leukocyte detect abnormalities soon after the injection and image not only reticuloendotelial system but also visualize urinary tract, bowl and gall bladder. Limitation includes the short half life of 99mTc and delayed bone marrow imaging (2 to 3 days between leukocyte imaging and bone

Platelets; an important part of thrombus formation, when **labeled with 111In** can follow simple cell migration mechanism to incorporate inside active thrombus formation so that easily picturize the thrombus formation**. Heat damaged 99mTc-RBCs** taken up for the examination of splenic nodule tissue formed after splectomy. During circulation of old and new RBCs, the old and damaged one was sequenter in the spleen. In same way heat damaged labeled RBCs sequenter inside spleen and

Tumor cells have higher metabolic rate as compare to the normal body cells, this upreglate the metabolism of cells and trap more molecule per gram than normal somatic cells. Through different metabolic ways like enhanced glucose metabolism for harvesting more energy. Following mechanism involved in proliferating cell

**3. Infection imaging agents based on metabolic activities**

• Thymidine kinase activity and folic acid synthesis

happen if the same metabolism used for imaging cell?

• Imaging cell micro-environment through Hypoxia and acidic pH

Cancerous cells proliferate rapidly and get more energy to fulfill physiological activities. Glucolysis is the preliminary energy driving metabolism. What would

tamination that may be tainted with hepatitis B, C or HIV.

**104**

An analogous molecule of glucose but not sugar it has one oxygen atom less than glucose. Fluorine (F- 18), a cyclotron based radionuclide labeled with glucose analogous (deoxyglucose) through nucleophilic reaction with mannos triflate (precursor) [2]. **18F-FDG (fluorodeoxyglucose**) practice for clinical oncology since 1980s [46]. The fluorodeoxyglucose participate and transport inside cell by following the same pathway as glucose through glucose transporter; GLUT-1. This glucose transpoter GLUT-1 release in stress condition and a member of glucose regulating protein [45]. As said earlier deoxyglucose is a glucose analogous, so this analogous molecule metabolized by the same pathway as glucose and was trapped in place of glucose molecule and get phosphorylated (glycolysis) as shown in **Figure 12**.

Glucose-6-phosphate further participate in glycolysis but FDG-6- phosphate cannot metabolized (not being the subsequent substrate) as glycolytic enzyme glucose-6-phosphate isomerase (hexokinase) has strict structural and geometric demands so fluorine substituted; 2-oxy-2-fluoro-D-glucose trapped and accumulate inside cell cytoplasm (metabolic trapping) [44]. Remember that glucose and FDG compete for the same transporter GLUT-1, so higher glucose level may lower the uptake of FDG. The enzyme hexokinase may convert back fluoro-6-phosphate to FDG but cancerous cell have very low amount of this enzyme so this trapped molecule (18FDG-6-PO4) aid in-vivo study of homeostatic system without disturbing their function. 18F-FDG is presently the most widely used PET tracer for imaging non-invasive malignant tissues that highly metabolized glucose [45].

The 18F-fluorodeoxyglucose participate in imaging of osteomyelitis, spinal infections, endocarditis, infected joint prosthesis, diagnose FUO and diabetic foot infection. Limitation regarding 18F-FDG use that it cannot differentiate between infection and sterile inflammation.
