Active Transport

Active Transport involves use of a normally operative energy-dependent metabolic pathway in the body to move a radiopharmaceutical across a cell membrane and into the cell. For example, thyroid uptake of radioiodide is by active transport. The first step involves trapping of the iodide; it then undergoes intermediate syntheses involving a thyroglobulin intermediate and is ultimately converted into T₃ and T₄ by the process of organification. Initial localization following IV injection is in the thyroid, stomach, parotids, and choroid plexus; ultimately, the iodide is stored in the thyroid as thyroxines with a t_biol of approximately 3 weeks or cleared through the kidneys.

Myocardial perfusion imaging is routinely performed with Tl-201 in the form of thallous ion (Tl¹⁺). This involves utilization of the normally operative metabolic pathway for handling potassium since Tl¹⁺ is a potassium analog and is therefore handled efficiently by the well-documented ATPase-driven Na/K pump mechanism. Initial localization of Tl¹⁺ following IV injection is in the heart, liver, and muscle; ultimately it is recycled so very little is cleared through the kidneys. The whole body tbiol is approximately 10 days. This use of Tl¹⁺ is also an excellent example of active transport.

Renal imaging with I-131 o-iodohippurate or Tc-99m MAG3 for tubular secretion studies is also an example of active transport. These compounds are processed predominantly by tubular secretory function. Approximately 80+% of both hippuran and MAG3 is removed from the blood stream by tubular secretion; the remainder is by GFR. Imaging is typically begun immediately post injection and acquisition is divided into frames, permitting generation of renogram curves.

Uptake by brain localizing radiopharmaceuticals such as Tc-99m HMPAO, Tc-99m ECD, I-123 IMP or I-123 HIPDM, probably also falls under the category of Active Transport. While the mechanism of cerebral uptake has not been completely elucidated, it appears to be related to "pH Shift"; that is, intracerebrocellular pH is lower than blood pH and these agents, which have the unique ability to penetrate an intact blood-brain barrier, are immobilized in brain cells due to this small change in pH of the compound. Their uptake may also be receptor-related. These agents basically take a "snapshot" of cerebral blood flow at the time of injection since brain uptake is very rapid and irreversible. Initial localization in the brain is in the range of 4-9%; often there is significant localization in the lungs, requiring shielding for performance of SPECT studies. Brain uptake remains essentially constant for the duration of the study.

Imaging tumors of neuroendocrine origin also probably falls under the category of active transport although metabolic incorporation is perhaps a better name for the mechanism. The I-123 or I-131 m-iodobenzylguanidine (mIBG) injected is so similar structurally to guanethidine, the precursor of epinephrine, that these tumors, which include pheochromocytomas, neuroblastomas, paragangliomas, carcinoid type tumors, and medullary hyperplasia, attempt to use it as a substrate for synthesis of hormones. Because of this attempt at chemistry by the tumors, this material accumulates within them. Since conversion of the mIBG to epinephrine doesn't take place, however, the accumulated tracer activity simply increases in the tumor as a function of time. By 24-48 hr, several % of the injected dose localizes in the tumors; a small amount accumulates in the liver; and parotids and normal adrenals are usually visualized. The remainder is excreted by the kidneys. Depending upon the radioisotope used, initial imaging is typically performed 24-48 hr post injection. In selected patients, imaging may be performed at 72 hr with the I-131 compound.