Radiolabeled agents for Brain Perfusion SPECT

Iodine-123 is a radionuclide with a relatively short half-life of approximately 13 hours. Its emitted gamma photon has an energy of 159 KeV (Kilo-electron Volts), compatible with current imaging systems. I-123 has been labeled to several ligands that have been applied clinically.

I-123-isopropyliodoamphetamine (IMP)

I-123-IMP is highly lipophilic, and moves across the blood brain barrier with almost complete extraction during a single passage through the cerebral circulation. Even though the amine has a low affinity for blood brain barrier transport sites, the speed of uptake is very fast compared to glucose. It distributes proportionally to rCBF under normal physiologic conditions and over a wide range of flow, but may be decreased with low plasma pH as in respiratory acidosis, metabolic acidosis or cerebral ischemia.

It has a relatively high first-pass brain extraction of about 85% and reaches 75% of peak activity within 15 to 20 minutes. The sequestration of basophilic amines by the brain and lung is a saturable process and is mediated by non-specific mechanisms. IMP is sequestered by binding to a high capacity cytoplasmic system, presumably a protein widely dispersed in organs and most abundant in the lung. Initial clearance of the tracer from the brain is balanced by continued brain uptake from the plasma due to slow release of the tracer from the lungs. As a result, the brain activity remains relatively constant from 20 to at least 60 minutes post-injection. Subsequently the intracerebral distribution changes because of greater clearance from the cortex than from white matter.

Most brain tumors extract little IMP, probably because there is a deficiency in the lipophilic sequestration system. Cerebral metastases from malignant melanoma and oat cell tumors do take up the tracer avidly, however, particularly if they are actively metabolizing amphetamine precursors.

IMP uptake is decreased under anesthesia perhaps because there is a decrease in the number of perfused capillaries (about 50% of normal) under pentobarbital anesthesia.

In the monkey, IMP accumulates rapidly within the brain reaching 6-9% of the injected dose at 1 hour, with some evidence of washout by 4 hours. By 24 hours, only 2% of the injected dose remains in the brain. The gray to white matter ratio is constant for the first hour, falling slightly by 4 hours and reversing by 24 hours. Either IMP is extracted from the blood by the gray matter before reaching white matter, or IMP has a faster turnover in gray matter than in white matter, or the coefficient of extraction of IMP is different in gray and white matter.

In the human, brain uptake of IMP is rapid, reaching 45% of the maximum brain activity by 2 minutes and 6-9% of the injected dose by 30 minutes. The clearance of the tracer from the brain is balanced by slow release of IMP from the lungs. Thus brain activity remains constant from 20 minutes to at least 60 minutes after injection. The gray to white matter activity ratio remains almost constant during that time. By 24 hours, the gray/ white matter activity ratio has reversed, and activity is higher in the white matter.

IMP concentration in brain tissue immediately after an intravenous bolus injection is a reflection of blood flow. As the distribution of the tracer equilibrates between brain and blood over time, the brain concentration becomes a function of the partition coefficient. IMP washes out of the brain relatively slowly.

I-123-IMP is prelabeled by the commercial supplier, resulting in some time constraints due to isotope decay. The standard injected dose is 3 to 6 mCi. Uptake of unbound I-123 by the thyroid gland is blocked by Lugol's solution given orally before injection.