Diagnosis

Clinical symptoms upon presentation of glioma vary by tumour type. Headaches resulting from increased intracranial pressure is a common symptom for all tumour types. Hemiparesis and mental status abnormalities are more common in glioma than in other brain tumours, but are not definitive and can be indicative of non-neoplastic conditions. Seizures occur more frequently with low-grade tumours than with high-grade tumours.

Diagnosis with ¹²³I-ACD-101 (SPECT)
Diagnosis of glioma is currently corroborated using a combination of structural and functional imaging modalities, depending on institutional availability. Final diagnosis is made by histology.
Structural imaging with magnetic resonance imaging (MRI in connection with contrast agent (gadolinium) is the structural imaging methodology of choice, being able to detect not only tumour, but also the oedema surrounding many gliomas. Gadolinium enhancement is based on a disruption of the blood brain barrier (BBB) in the area of tumour growth. It is well established however, that BBB disruption is a late event in tumour development. Consequently a diagnostic procedure based on this is inherently insensitive both with regard to image true tumour extensions and to detect them at the earliest possible stage.

To overcome this problem molecular imaging with SPECT (single photon emission tomography) or PET (positron emission tomography) using radioactively labelled metabolic substrates (radiotracers), preferentially enriched by tumour compared to normal tissue have considerably increased sensitivity of glioma diagnostics.
18F-Fluoro-deoxy-glucose (18F-FDG), the most widely used PET tracer in oncology which is commercially available from different manufacturers across Europe, has only limited diagnostic value as many tumours especially those with low histological grade are iso- or hypometabolic, i.e. show lower or comparable uptake, compared to healthy brain. Sensitivities can be as low as 56 - 65 %. Nevertheless, FDG continues to be the clinical standard in many countries.


Diagnosis with ¹²⁴I-ACD-101 (PET)
In contrast, amino acid tracers such as 11C-methionine PET show sensitivities of around 90% even in tumours which can not be detected with 18F-FDG PET. Besides 11C-methionine other amino acid derivatives such as 18F-fluoro-ethyl-tyrosine (18F-FET) as PET tracer, and [123I]iodo-methyl-tyrosine as a SPECT tracer have been described to have superior sensitivity than 18F-FDG PET in the diagnosis of glioma.

Today, 11C-methionine and increasingly 18F-FET PET aremost widely used imaging methodologies to detect low-grade and high-grade gliomas with a sensitivity of > 90% , irrespective of whether the BBB is disrupted or not. The use of 11C-methionine in clinical medicineis, due to the short half life of 11C (20 min), restricted to only about 20 academic PET facilities in Europe operating a cyclotron to manufacture 11C-methionine on site. Also, 18F-FET is not available in many countries at present. An amino acid-based radiotracer combining the sensitivity of 11C-methionine or 18F-FET with general availability due to a longer half life (4 days), suitable for current molecular imaging with PET/CT or PET / MRI would be of considerable help to neuro-oncological medicine to improve early diagnosis of glioma and to contribute to therapeutic research for this deadly condition.
124I-ACD-101 fulfills these requirements, and is available for research purposes in GMP quality.