Radiation dosimetry and biodistribution of the beta-amyloid plaque imaging tracer ¹¹C-BTA-1 in humans

Summary

Aim: [N-methyl-¹¹C]2-(4'-(methylaminophenyl)-benzothiazole (¹¹C-BTA-1) is a thioflavin-T derivative that has been one of the promising PET tracers for imaging of amyloid plaque distribution in the Alzheimer patients brain in vivo. The biodistribution and dosimetry of this tracer in humans is presented and compared to the results of a previous dosimetry and biodistribution study of another thioflavin-T derivative [N-methyl-¹¹C]2-hydroxy-(4'-(methylaminophenyl)- benzothiazole (¹¹C-OH-BTA-1) in baboons. Methods: Five subjects underwent 2D dynamic PET imaging. Source organs were segmented using a semiautomatic algorithm based on clustering. Residence times for each source organ were determined by analytical integration of an exponential fit of the time activity curves. Finally organ doses were estimated using the software OLINDA/EXM. Results: The administration of 286 ± 93 MBq ¹¹C-BTA-1 was well tolerated by all subjects. Effective radiation dose was 4.3 μSv/MBq, range 3.6–5.0 μSv/MBq. In four of the five subjects the liver, in one of the subjects the gallbladder was the critical organ. Conclusion: The radiation burden of a single dose of 300 MBq ¹¹C-BTA-1 is within the accepted limits for research purpose. In contrast to the previous non-human primate study revealing the gallbladder as the critical organ for ¹¹C-6-OH-BTA-1, we found the liver as the critical organ in humans using ¹¹C-BTA-1. Possible explanations may be (1) a reduced bile concentration of ¹¹C-BTA-1 due to the absent OH-group or (2) a different hepatic metabolism of thioflavin derivatives in human and baboon.

Zusammenfassung

Ziel: Das Thioflavinderivat [N-Methyl-¹¹C]2-(4'-(methylaminophenyl)-benzothiazol (¹¹C-BTA-1) wurde als einer der viel versprechendsten PET-Tracer zur in vivo Darstellung der Amyloid-Plaques im Gehirn von Alzheimer-Patienten vorgestellt. Hier präsentieren wir die Biodistribution und Dosimetrie dieses Tracers im Menschen und vergleichen die Ergebnisse mit einer anderen Studie welche die Biodistribution und Dosimetrie des Thioflavinderivats [N-Methyl- ¹¹C]2-hydroxy-(4'-(methylaminophenyl)-benzothiazol (¹¹C-OH-BTA-1) am Pavian untersucht hat. Methoden: An fönf Probanden wurde eine 2D-PET-Bildgebung durchgefuhrt. Die verschiedenen, sichtbar anreichernden Organe wurden mittels eines halbautomatischen Algorithmus segmentiert. Die Verweildauer für die segmentierten Organe wurde mittels einer analytischen Integration des exponentiellen Fits der Zeit-Aktivitäts-Kurven bestimmt. Schließlich wurden die Organdosen berechnet (OLINDA/ EXM). Ergebnisse: Die Gabe von 286 ± 93 MBq ¹¹C-BTA-1 wurde von allen Probanden gut toleriert. Die effektive Strahlungsdosis betrug 4.3 μSv/MBq, Spannweite 3.6–5.0 μSv/MBq. Bei vier Probanden war die Leber, bei einem die Gallenblase das kritische Organ. Schlussfolgerungen: Die Strahlenbelastung einer Einzeldosis von 300 MBq ¹¹C-BTA-1 liegt innerhalb der für wissenschaftliche Zwecke akzeptierten Grenzen. Im Gegensatz zu einer vorangegangenen Primaten-Studie, die für ¹¹C-6-OH-BTA-1 die Gallenblase als das kritische Organ bestimmt hat, ergab sich im Menschen für ¹¹C-BTA-1 die Leber als das kritische Organ. Erklärungen hierfür sind: (1) eine reduzierte biliare Konzentration von ¹¹C-BTA-1 auf Grund der abwesenden OH-Gruppe oder (2) ein unterschiedlicher hepatischer Metabolismus der Thioflavinderivate bei Mensch und Pavian.

Keywords

BTA-1 - PET - Alzheimer - biodistribution - dosimetry

Schlüsselwörter

BTA-1 - PET - Alzheimer-Erkrankung - Biodistribution - Dosimetrie

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