Imaging of dopamine transporter with [18F]LBT-999: initial evaluation in healthy volunteers.

BACKGROUND: The aim of this study was to evaluate in healthy human brain the distribution, uptake, and kinetics of [18F]LBT-999, a PET ligand targeting the dopamine transporter, to assess its ability to explore dopaminergic innervation, using a shorter protocol, more convenient for patients than currently with [123I]ioflupane. METHODS: After intravenous injection of [18F]LBT-999, 8 healthy subjects (53-80y) underwent a dynamic PET-scan. Venous samples were concomitantly obtained for metabolites analysis. Time activity curves (TACs) were generated for several ROIs (caudate, putamen, occipital cortex, substantia nigra and cerebellum). Cerebellum was used as reference region to calculate binding potentials (BPND). RESULTS: No adverse events or detectable pharmacological effects were reported. [18F]LBT-999 PET revealed a good cerebral distribution, with an intense and symmetric uptake in both putamen and caudate (BPND of 6.75±1.17 and 6.30±1.17, respectively), without other brain abnormal tracer accumulation. Regional TACs showed a plateau from the maximal uptake, 20min pi, to the end of the acquisition for both caudate and putamen, whereas uptake in substantia nigra decreased progressively. A faster clearance and lowest BPND values were observed in both cortex and cerebellum. Ratios to the cerebellum exhibit value of about 3 in substantia nigra, close to 10 for both caudate and putamen, and remained around the value of 1 in cortex. The parent fraction of [18F]LBT-999 in plasma was 80%, 60% and 45% at 15, 30 and 45 min pi, respectively. CONCLUSIONS: These findings support the usefulness of [18F]LBT-999 for a quantitative clinical evaluation of presynaptic dopaminergic innervation.

The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use.

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2ß-carbomethoxy-3ß-(4'-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease.

Estimation of the added value of 99mTc-HMPAO-labelled white blood cell scintigraphy for the diagnosis of infectious foci.

BACKGROUND: Leucocytes scintigraphy (LS) is an in-vivo imaging technique investigating infectious foci, performed in our nuclear medicine department after a 99mTc-bisphophonates bone scintigraphy (BS) or an 18F-FDG-PET, in osteoarticular or vascular localizations, respectively. The aim of this study was to reassert the relevance of LS in the diagnostic of occult infections and its impact in therapeutic management. METHODS: A 45-month retrospective study (2012-2015), including 34 patients, was conducted. Patients who underwent LS were identified and classified according to the location of the suspected infection and the feature of first-line imaging exploration. The final diagnosis (infected or non-infected lesion) was established regarding patients' follow-up care, including clinical, biological biomarkers and therapeutic interventions. Sensitivity and specificity were calculated for each imaging modality. RESULTS: LS were conducted for exploration of joint prosthesis (N.=14), vascular prosthesis (N.=7), bone infection or osteitis (N.=8), algoneurodystrophia (N.=2), symphisis infection (N.=1), acute infection on chronicle inflammation (N.=1), and cancer (N.=1). All patients underwent a previous imaging exploration: BS (N.=20, 59%), 18FDG-PET (N.=10, 29%), or another exploration (N.=4, 12%). The sensitivity and specificity of BS were 67% and 36%, respectively, and 100% and 50% for 18FDG-PET, evidencing the lack of specificity of these approaches. Fourteen LS were positive (41%), with sensitivity, specificity and diagnostic accuracy of 85%, 86% and 85%, respectively. CONCLUSIONS: Despite a long, delicate, and costly radiopharmaceutical and nuclear imaging process, the high specificity of LS supports its qualitative added value in the diagnosis of infectious foci, by improving clinical and therapeutic patient's outcomes.