Initial evaluation of the feasibility of single photon emission tomography with p-[123I]iodo-L-phenylalanine for routine brain tumour imaging

Abstract

p-[123I]iodo-L-phenylalanine (IPA) is a recently described radiopharmaceutical which is highly accumulated in gliomas. The present investigation was designed to evaluate the feasibility of single photon emission tomography (SPET) with IPA to image brain tumours under routine clinical conditions. Using a dual- and a triple-headed SPET camera, whole-body kinetic and brain SPET, as well as plasma, urinary and dosimetric analysis were determined in four patients with gliomas after intravenous injection of IPA. Results obtained by IPA SPET were retrospectively compared with histopathology, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose. Tumour lesions were clearly demonstrated by IPA SPET at 30 min, 1h and 4.5h post-injection, even in patients with low grade gliomas. In patients with glioblastoma, excellent visualization of the tumour was possible even at 7h p.i., indicative of the high retention of the radiopharmaceutical in cerebral gliomas. Analysis of the radioactivity in plasma and urine attested to the high in vivo stability of IPA. Blood clearance was rapid (> 65% after 10 min) and IPA was excreted predominantly by the kidneys, the urinary radioactivity excretion ranging from 27% at 1h to 54% of injected doses at 5h p.i. The average effective dose for adults was estimated to be 0.0152mSv*MBq(-1), leading to an effective dose of 3.8mSv in a typical brain SPET investigation with 250 MBq IPA. This result strongly suggests that IPA is a potentially valuable brain tumour imaging agent for widespread clinical studies with SPET. Its high specific tumour uptake and retention even in low grade gliomas represent a major advantage compared to presently available SPET radiopharmaceuticals. Moreover, the radiation dose estimates indicate that clinical use of IPA will result in acceptable radiation dose levels in humans.

Efficacy of Systemic Radionuclide Therapy with p-131I-Iodo-l-Phenylalanine Combined with External Beam Photon Irradiation in Treating Malignant Gliomas

“…Moreover, previous investigations of 131 I-IPA monotherapy found no histomorphologic abnormalities in the liver, kidneys, and thyroid of treated animals, and no rat had clinical signs of malfunction of any organ (24). Additionally, prior biodistribution studies and radiation dose estimates based on studies in animals and humans revealed that 123 I-IPA-131 I-IPA is exclusively eliminated by urine, and the highest absorbed doses were determined in the urinary bladder wall and in the kidneys (18,21,37,38). Radioactivity accumulation in bone marrow, the urogenital system, and the thyroid gland is rather tolerably low.…”

“…The iodinated amino acids p-123 I-iodo-L-phenylalanine ( 123 I-IPA) and p-124 I-iodo-L-phenylalanine have been used clinically for this purpose (18)(19)(20). Both these phenylalanine derivatives actively cross the blood-brain barrier after intravenous administration and accumulate specifically in gliomas, presumably via the amino acid transporters L and ASC (system ASC amino acid transporter for neutral amino acids), which are overexpressed in malignant glioma cells (21)(22)(23).…”

“…A specific accumulation and prolonged retention of the radiopharmaceuticals were demonstrated clinically for low-grade and highgrade gliomas alike. At the same time, the uptake of these agents in normal brain parenchyma and nonneoplastic lesions remained moderate (18)(19)(20). Therefore, we postulated that when administered systemically, L-phenylalanine that was conjugated to a a-or b-emitting radionuclide such as 211 At or 131 I could selectively deliver an effective radiation dose to malignant glioma cells.…”

Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[76Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging

“…System L is active at the blood–brain barrier (BBB) which is desirable for imaging gliomas and other brain tumors with relatively intact BBBs that are not visualized using contrast enhancement on CT or MRI. 31–33 A number of amino acid based system L substrates have been developed including O -(2-[ 18 F]fluoroethyl)- l -tyrosine (FET), 12–15 6-[ 18 F]fluoro-3,4-dihydroxy- l -phenylalanine (FDOPA), 16,17 3-[( 123 )I]iodo- l - α -methyltyrosine (IMT), 34 and 4-[ 123/124/131 I]iodo- l -phenylalanine (IPA), 35–37 all of which have been used for imaging of gliomas. In addition to providing distinct metabolic information, these amino acids have less uptake in the normal brain and inflammatory tissues compared to [ 18 F]FDG.…”

Brain tumour recurrence: brain single-photon emission computerized tomography, PET and proton magnetic resonance spectroscopy

“…Concerning the development of new g-emitting tracers it has to be mentioned that the novel radiocompound p-123 I-iodo-L-phenylalanine has been proposed to investigate low-grade and high-grade glioma [16], although data on recurrence are not still available.…”