Microscale radiosynthesis, preclinical imaging and dosimetry study of [18F]AMBF3-TATE: A potential PET tracer for clinical imaging of somatostatin receptors.

Abstract

BACKGROUND:

Peptides labeled with positron-emitting isotopes are emerging as a versatile class of compounds for the development of highly specific, targeted imaging agents for diagnostic imaging via positron-emission tomography (PET) and for precision medicine via theranostic applications. Despite the success of peptides labeled with gallium-68 (for imaging) or lutetium-177 (for therapy) in the clinical management of patients with neuroendocrine tumors or prostate cancer, there are significant advantages of using fluorine-18 for imaging. Recent developments have greatly simplified such labeling: in particular, labeling of organotrifluoroborates via isotopic exchange can readily be performed in a single-step under aqueous conditions and without the need for HPLC purification. Though an automated synthesis has not yet been explored, microfluidic approaches have emerged for 18F-labeling with high speed, minimal reagents, and high molar activity compared to conventional approaches. As a proof-of-concept, we performed microfluidic labeling of an octreotate analog ([18F]AMBF3-TATE), a promising 18F-labeled analog that could compete with [68Ga]Ga-DOTATATE with the advantage of providing a greater number of patient doses per batch produced.

METHODS:

Both [18F]AMBF3-TATE and [68Ga]Ga-DOTATATE were labeled, the former by microscale methods adapted from manual labeling, and were imaged in mice bearing human SSTR2-overexpressing, rat SSTR2 wildtype, and SSTR2-negative xenografts. Furthermore, a dosimetry analysis was performed for [18F]AMBF3-TATE.

RESULTS:

The micro-synthesis exhibited highly-repeatable performance with radiochemical conversion of 50 ± 6% (n = 15), overall decay-corrected radiochemical yield of 16 ± 1% (n = 5) in ~40 min, radiochemical purity >99%, and high molar activity. Preclinical imaging with [18F]AMBF3-TATE in SSTR2 tumor models correlated well with [68Ga]Ga-DOTATATE. The favorable biodistribution, with the highest tracer accumulation in the bladder followed distantly by gastrointestinal tissues, resulted in 1.26 × 10-2 mSv/MBq maximal estimated effective dose in human, a value lower than that reported for current clinical 18F- and 68Ga-labeled compounds.

CONCLUSIONS:

The combination of novel chemical approaches to 18F-labeling and microdroplet radiochemistry have the potential to serve as a platform for greatly simplified development and production of 18F-labeled peptide tracers. Favorable preclinical imaging and dosimetry of [18F]AMBF3-TATE, combined with a convenient synthesis, validate this assertion and suggest strong potential for clinical translation.

• Authors: Ksenia Lisova, Maxim Sergeev, Susan Evans-Axelsson, Andreea D Stuparu, Seval Beykan, Jeffrey Collins, Jason Jones, Michael Lassmann, Ken Herrmann, David Perrin, Jason T Lee, Roger Slavik, R Michael van Dam
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 61 Pg. 36-44 (06 2018) ISSN: 1872-9614 [Electronic] United States
• PMID: 29747035 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• AMBF3-TATE
• Boron Compounds
• Fluorine Radioisotopes
• Radioactive Tracers
• Receptors, Somatostatin
• Fluorine-18
• Octreotide

Topics

• Animals
• Boron Compounds (chemistry)
• Cell Line, Tumor
• Fluorine Radioisotopes
• Lab-On-A-Chip Devices
• Mice
• Octreotide (analogs & derivatives, chemistry)
• Positron Emission Tomography Computed Tomography
• Radioactive Tracers
• Radiochemistry (instrumentation)
• Radiometry
• Receptors, Somatostatin (metabolism)