Quantitative Kinetics of [124I]FIAU in Cat and Man

Quantitative Kinetics of [¹²⁴I]FIAU in Cat and Man

Andreas Jacobs, Ines Bräunlich, Rudolf Graf, Martin Lercher, Takayuki Sakaki, Jürgen Voges, Volker Hesselmann, Wolfgang Brandau, Klaus Wienhard and Wolf-Dieter Heiss

Max-Planck-Institute for Neurological Research, Center for Molecular Medicine, and Departments of Neurology, Stereotactic Neurosurgery, and Radiology, University of Cologne, Cologne; and Department of Nuclear Chemistry and Radiopharmacy, University of Essen, Essen, Germany

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FIGURE 1. Multitracer PET imaging of ventilated cat allows functional analysis of various tissues of total body at same physiologic status over prolonged period of time using specific radiotracers. Coregistered MRI allows anatomic delineation of various organs. In healthy cat brain, physiologic glucose ([¹⁸F]FDG) and oxygen ([¹⁵O]O₂) consumption with normal cerebral blood flow ([¹⁵O]H₂O) is not accompanied by significant uptake of amino acid ([¹¹C]MET) or nucleoside analog ([¹²⁴I]FIAU).

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FIGURE 2. For dynamic evaluation of [¹²⁴I]FIAU influx and washout in cats, ROI analysis focused on organs such as brain (1), heart (2), lung (3), muscle (4), liver (5), stomach and spleen (6), kidney (7), intestine (8), and bladder (9). Stomach and intestine could not be differentiated and were combined into one region. Coregistered FDG PET reveals glucose consumption in brain and heart and excretion of tracer into bladder. Coregistered [¹⁵O]H₂O PET shows high activities in well-perfused organs such as brain, heart, liver, and kidneys.

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FIGURE 3. Analysis of quantitative kinetics of [¹²⁴I]FIAU in various organs of cats early (A) and late (B) after systemic administration of 37 MBq [¹²⁴I]FIAU. Values are averaged over three animals. Brain showed lowest [¹²⁴I]FIAU uptake of all organs throughout entire measurement. Brain symbols (•) represent PET frames acquired sequentially. For clarity in graphs, not all symbols for each frame are depicted for other organs. p.i. = after injection.

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FIGURE 4. Multitracer PET and MRI of 50-y-old male patient with recurrent glioblastoma in left parieto-occipital lobe. T1-weighted MR image shows large subcortical edema within left hemisphere surrounding contrast-enhancing tumor mass. Tumor shows increased [¹¹C]MET uptake (3.1-fold higher than corresponding contralateral temporal region), high glucose consumption (37.3 µmol/100 g/min), and deactivation of surrounding cortex (62.1% of corresponding contralateral region). After systemic administration of 77 MBq [¹²⁴I]FIAU, dynamic emission sequence over 68 h shows high FIAU accumulation within tumor, scalp, and soft tissue within first hour after injection (p.i.). At later times (8–24 h after injection), substantial FIAU uptake was also observed in peritumoral edematous areas. Washout of FIAU from these regions was slow. Substantial uptake of FIAU in contralateral gray and white matter was not observed.

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FIGURE 5. Quantitative kinetics of [¹²⁴I]FIAU in plasma, scalp, tumor, paratumoral area, gray matter, and white matter of 50-y-old male patient with recurrent glioblastoma. Maximum values are reached in tumor and scalp regions within 5–10 min after injection. FIAU washout from tumor and scalp follows similar kinetics. Gray and white matter [¹²⁴I]FIAU uptake values are always much lower than those in tumor. Symbols represent PET frames acquired sequentially. For clarity in graph, symbols for first 11 frames acquired during first hour after [¹²⁴I]FIAU injection are omitted. Curves are model fits to data.

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FIGURE 6. Patlak plots of FIAU uptake in various tissues of 50-y-old male patient with recurrent glioblastoma show fast initial uptake of FIAU in tumor and scalp but no FIAU accumulation or trapping in any tissue. Curves are model fits to data.