**2.8 Filtration**

Filtration is denoted as a significant case of diffusion in which carrier molecules are compelled to progress by an osmotic or hydrostatic pressure gradient through several channels and pores. The significant example of this process explained is by glomerular filtration of kidney. Radiopharmaceuticals are effectively employed in renal imaging and in the determination of renal morphology or renal functioning. Two physiological mechanisms such as glomerular filtration and tubular secretion are accountable for renal imaging. Agents cleared by glomerular filtration are further utilized in investigating the glomerular filtration rate (GFR) [19].

**99**

**Figure 8.**

*kidney [19].*

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

or carrier molecules [37].

depicted as shown in **Figure 8**.

as shown in **Figure 9**.

**2.9 Active transport**

carriers are engaged [19].

There are two factors that are primarily concerned for the glomerular filtration of kidney comprising radiopharmaceuticals. First factor is the availability, only those molecules are liable for filtration that are freed in plasma and are not protein bounded. Second factor required for glomerular filtration is the pore size versus molecular size. Usually, only small hydrophilic molecules having a size less than

Some other factors are also involved in this glomerular filtration mechanism. Some pressure gradient or force is necessity for filtration while in the case of glomerular filtration, this specified force is provided by blood pressure however it does not demand any indigenous involvement of external output or energy. Moreover, filtration is non-selective due to the non-involvement of any receptors, transporters

Various radiopharmaceuticals are excreted partially by glomerular filtration, but the radiopharmaceutical most employed for renal imaging glomerular function is Tc-99 m DTPA. Renal DTPA can be determined from estimating the activity in multiple or single blood samples, the elimination of activity from tissue or blood and from the emergence of tracer particles in urine [19]. Example of Filtration process is

Some other radiopharmaceuticals excreted indigenously during glomerular filtration are 99mTc- MAG3 and EC (ethylene di-cysteine) for tubular secretion, 131I and 123I for Tubular (80%) and glomerular (20%), 99mTc-DMSA for cortical binding (50%), and 99mTc-GHA for cortical binding (20%) and glomerular filtration (80%)

Active transport is carrier mediated, metabolic, energy dependent pathway in a body to move forward a radiopharmaceutical across a cell membrane into a cell. The energy utilized during this reaction comes from ATP that allows the transport of molecules against a concentration gradient. It is carrier selective, which explicates fitting of small number of molecules into a specific carrier and makes it possible to accomplish saturation i.e. maximum response provided when all the

*Pre-treatment was done with captopril (an ACE inhibitor used for decreasing pressure on blood vessels), glomerular filtration of Tc-99 m DTPA is decreased as seen in the left kidney (arrow). Captopril employed, blocked the compensation mechanism triggered by left kidney ensuring a decreased pressure in the left* 

5000 are capable of disseminating through glomerular pores [36].

**Figure 7.** *Systematic representation of chemisorption of 99mTc-PYP [35].*

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

*Medical Isotopes*

**2.8 Filtration**

post injection [33].

*2.7.1 Chemisorption mechanism of 99mTc-PYP*

radiopharmaceutical uptake in bone is low, so imaging starts after three hours of

99mTc-PYP is used for the acute myocardial infarction imaging is an example of Chemisorption mechanism of localization. Myocardial infarction starts when myocardial cells turn out to be necrotic, calcium ions influx create into the cells. Circulating phosphate ions present in body reacts with the Ca2+ ions and Ca3 (PO4)2 crystals are formed. Resulting calcium phosphate crystals formed hydroxyapatite present on bone tissues. 99mTc-PYP binds irreversibly and avidly to calcium phosphate crystals at the infarct periphery where some perfusion is maintained as shown in **Figure 7**. After two hours of post injection imaging takes place [34].

Filtration is denoted as a significant case of diffusion in which carrier molecules are compelled to progress by an osmotic or hydrostatic pressure gradient through several channels and pores. The significant example of this process explained is by glomerular filtration of kidney. Radiopharmaceuticals are effectively employed in renal imaging and in the determination of renal morphology or renal functioning. Two physiological mechanisms such as glomerular filtration and tubular secretion are accountable for renal imaging. Agents cleared by glomerular filtration are

further utilized in investigating the glomerular filtration rate (GFR) [19].

**98**

**Figure 7.**

*Systematic representation of chemisorption of 99mTc-PYP [35].*

There are two factors that are primarily concerned for the glomerular filtration of kidney comprising radiopharmaceuticals. First factor is the availability, only those molecules are liable for filtration that are freed in plasma and are not protein bounded. Second factor required for glomerular filtration is the pore size versus molecular size. Usually, only small hydrophilic molecules having a size less than 5000 are capable of disseminating through glomerular pores [36].

Some other factors are also involved in this glomerular filtration mechanism. Some pressure gradient or force is necessity for filtration while in the case of glomerular filtration, this specified force is provided by blood pressure however it does not demand any indigenous involvement of external output or energy. Moreover, filtration is non-selective due to the non-involvement of any receptors, transporters or carrier molecules [37].

Various radiopharmaceuticals are excreted partially by glomerular filtration, but the radiopharmaceutical most employed for renal imaging glomerular function is Tc-99 m DTPA. Renal DTPA can be determined from estimating the activity in multiple or single blood samples, the elimination of activity from tissue or blood and from the emergence of tracer particles in urine [19]. Example of Filtration process is depicted as shown in **Figure 8**.

Some other radiopharmaceuticals excreted indigenously during glomerular filtration are 99mTc- MAG3 and EC (ethylene di-cysteine) for tubular secretion, 131I and 123I for Tubular (80%) and glomerular (20%), 99mTc-DMSA for cortical binding (50%), and 99mTc-GHA for cortical binding (20%) and glomerular filtration (80%) as shown in **Figure 9**.

#### **2.9 Active transport**

Active transport is carrier mediated, metabolic, energy dependent pathway in a body to move forward a radiopharmaceutical across a cell membrane into a cell. The energy utilized during this reaction comes from ATP that allows the transport of molecules against a concentration gradient. It is carrier selective, which explicates fitting of small number of molecules into a specific carrier and makes it possible to accomplish saturation i.e. maximum response provided when all the carriers are engaged [19].

#### **Figure 8.**

*Pre-treatment was done with captopril (an ACE inhibitor used for decreasing pressure on blood vessels), glomerular filtration of Tc-99 m DTPA is decreased as seen in the left kidney (arrow). Captopril employed, blocked the compensation mechanism triggered by left kidney ensuring a decreased pressure in the left kidney [19].*

#### **Figure 9.**

*Different mechanism of renal radiopharmaceutical excretion and uptake, including glomerular filtration, cortical binding and tubular secretion [38].*

Concentration of iodide in the thyroid gland is an eminent example of active transport. Iodide ions are conveyed into thyroid cells by the Na+ /I− symporter. Therefore, I-123 and I-131 (radioisotopes of iodine) are suitable radiopharmaceuticals to assess thyroid functioning [3]. Furthermore, Tc-99 m pertechnetate has almost same negative charge and ionic radius, hence it is too transported like iodide as shown in **Figure 10**.

It is highly significant that high concentrations of iodide (in the form of injections of iodinated contras media) in the blood, will competitively prevent thyroid uptake of these radiopharmaceuticals. Firstly, iodide is trapped producing an intermediate thyroglobulin and is eventually converted into T3 & T4. Preliminary, localized in thyroids, parotids and stomach and ultimately cleared through kidneys as shown in **Figure 10** [39].

#### **Figure 10.**

*(A) Regular uptake of Tc-99 m pertechnetate in thyroid (and salivary glands). (B) Absent uptake of thyroid (arrow) of Tc-99 m pertechnetate in an iodinated x-ray contrast media administered patient a few days earlier [19].*

**101**

**Figure 11.**

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

Glucose absorption from the GI tract into the blood and then reabsorption of glomerular-filtered glucose back into the blood by the distal renal tubules is another example of active transport. A sodium-dependent glucose cotransporter (SGLT) is employed to perform this function. Even though F-18 FDG is not voluntarily transported by SGLTs, glomerular filtered F-18 FDG residues in the urinary tract and flows to the bladder. Eventually, F-18 FDG do not perform the same function as

A third example of active transport is the Na+/K+ (sodium/potassium) pump,

*Following injection of F-18 FDG in a normal patient, there is high uptake in brain, variable uptake in heart* 

*(high uptake in this patient), and moderate uptake in liver, GI tract, and marrow [19].*

due to its significance in the heart muscle. Thallous chloride has extensively employed for myocardial perfusion scans. However, due to similar ionic size of thallous ion as potassium ion, it fits in place of potassium ion in sodium/potassium

glucose that is being reabsorbed into the blood [19] (**Figure 11**).

pump. Therefore, heart muscles reflect coronary perfusions.

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

*Medical Isotopes*

as shown in **Figure 10**.

*cortical binding and tubular secretion [38].*

**Figure 9.**

as shown in **Figure 10** [39].

Concentration of iodide in the thyroid gland is an eminent example of active

*Different mechanism of renal radiopharmaceutical excretion and uptake, including glomerular filtration,* 

Therefore, I-123 and I-131 (radioisotopes of iodine) are suitable radiopharmaceuticals to assess thyroid functioning [3]. Furthermore, Tc-99 m pertechnetate has almost same negative charge and ionic radius, hence it is too transported like iodide

It is highly significant that high concentrations of iodide (in the form of injections of iodinated contras media) in the blood, will competitively prevent thyroid uptake of these radiopharmaceuticals. Firstly, iodide is trapped producing an intermediate thyroglobulin and is eventually converted into T3 & T4. Preliminary, localized in thyroids, parotids and stomach and ultimately cleared through kidneys

*(A) Regular uptake of Tc-99 m pertechnetate in thyroid (and salivary glands). (B) Absent uptake of thyroid (arrow) of Tc-99 m pertechnetate in an iodinated x-ray contrast media administered patient a few days* 

/I−

symporter.

transport. Iodide ions are conveyed into thyroid cells by the Na+

**100**

**Figure 10.**

*earlier [19].*

Glucose absorption from the GI tract into the blood and then reabsorption of glomerular-filtered glucose back into the blood by the distal renal tubules is another example of active transport. A sodium-dependent glucose cotransporter (SGLT) is employed to perform this function. Even though F-18 FDG is not voluntarily transported by SGLTs, glomerular filtered F-18 FDG residues in the urinary tract and flows to the bladder. Eventually, F-18 FDG do not perform the same function as glucose that is being reabsorbed into the blood [19] (**Figure 11**).

A third example of active transport is the Na+/K+ (sodium/potassium) pump, due to its significance in the heart muscle. Thallous chloride has extensively employed for myocardial perfusion scans. However, due to similar ionic size of thallous ion as potassium ion, it fits in place of potassium ion in sodium/potassium pump. Therefore, heart muscles reflect coronary perfusions.

#### **Figure 11.**

*Following injection of F-18 FDG in a normal patient, there is high uptake in brain, variable uptake in heart (high uptake in this patient), and moderate uptake in liver, GI tract, and marrow [19].*

A second radiopharmaceutical is rubidium chloride which falls just below the potassium in periodic table has somewhat similar properties and fits in sodium/ potassium pump, thus utilizing for PET myocardial perfusion scans [39].
