*2.2.1 Mechanism of 99mTc-DTPA (diethylene triamine penta-acetic acid)*

A chief factor that has a key role in localization mechanism of radio tracer in brain region is barrier of blood and brain (brain–blood barrier/BBB). It is basically a uniform film of endothelial cells belonging to cerebral vessels, restricting the diffusion of lipophobic molecules, and allowing only lipophilic ones. Due to some physiological abnormalities, this barrier is interrupted allowing the diffusion of hydrophilic molecules in tissues of brain. Oxygen, electrolytes, CO, glucose, water and other smaller molecules diffuses passively in across barrier and use active mechanism to move in the neural cells, while immuno-globulins (large particles), many lipophobic radiotracers and other lipophobic (hydrophilic) particles cannot cross the barrier under normal circumstances but in situations when barrier is disrupted the radiotracers accumulate at the area of tumor/abnormality easily, showing a + scan.

A typical radiopharmaceutical for brain imaging by 99mTc-DTPA. Normally, it cannot diffuse across barrier easily because of its lipophobic nature (See **Figure 1(A)**), but in abnormalities like tumor and infections the barrier is disturbed, so, 99mTc-DTPA move passively across barrier and amass in the infected area of brain (See **Figure 1(B)**). Its biologic half-life is 1–2 hours, halftime for clearance of plasma is 70 minutes and in 24 hours 90% of the tracer is eliminated by urinary system.

10–20 millicurie of 99mTc-DTPA is injected intra-venously in the body and after an hour scanned via gamma cameras. If the scan shows no agglomeration of radiotracer in brain, it means that the barrier is intact, and the tracer was not able to past across the barrier. But if the scans show tracer concentration in the cells of brain it means the barrier is no more intact and is prevailed by anomalies. So, the tracer highlights the affected areas as hot-spots [7].

Other examples:

Other radiotracers that are involved in such type of study (that localize passively in brain) are 99mTc-glucoheptonate (GH),123I-serum albumin, technetium pertechnetate (99mTcO4 − ) [9], Thallous chloride Tl-201 [10, 11], Gallium citrate Ga-67 [12].

#### **Figure 1.**

*(A) Illustration of intact barrier in the brain cells that do not allow 99mTc-DTPA to diffuse, (B) disruption of barrier in the brain cells [8].*

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**Figure 2.**

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

Sestamibi is some-what similar to cationic 201Tl+

uphold this tracer are not prone to chemotherapy.

99mTc labeled cationic, lipophilic tracers like furifosmin, tetrofosmin and Sestamibi for myocardial perfusion imaging have been established. 99mTc-

the membrane only involves passive diffusion [13]. In start, it was assumed that the uptake of technetium labeled Sestamibi by the myocardial cells is primarily because of binding of lipid constituents to the membrane of cell. This ambiguity was later cleared that uptake was not because of membrane's binding to lipid constituent, instead the cellular entry is chiefly linked to mitochondria and its negative potential of inner membrane. About 90% of uptake was linked to mitochondria [14] (See **Figure 2(A)**). It was studied that the upholding of technetium labeled Sestamibi is not specific to tumor of some organs, rather it is a general mechanism. 99mTc- Sestamibi moves passively from blood to tumor and amass in the cancers that have low multidrug-resistant pump expression and more mitochondria making cancers susceptible to precise diagnosis. But in most cases, the resistance pump dominates over mitochondrial presence making cancers non-susceptible to 99mTc-Sestamibi, because the resistance pumps eject the radiotracer out of the cell [15]. So, the upholding status of this radiotracer reflects the membrane permeability of mitochondria and the mitochondrial potentials. Alterations due to cancers leads to dys-functioning of mitochondria that consequently cause decreased uptake of tracer [16] (See **Figure 2(B)**). The decreased upholding of technetium Sestamibi in the terms of chemotherapy (after chemotherapeutic session) is correlated to the over-expression of multidrug-resistant proteins. So, the cancers which do not

*(A) Normal binding of 99mTc- Sestamibi to mitochondria, (B) over-expression of resistance pump that quickly removes 99mTc-sestamibi out of cell, (C) effect of Bcl-2, an anti-apoptotic protein; that halts the binding of 99mTc-sestamibi to mitochondria [17].*

but Sestamibi transport across

*2.2.2 Mechanism of 99mTc- Sestamibi*

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