Jennifer Lynn Burkemper PhD, Presenter: Nothing to Disclose

Chaofeng Huang PhD, Abstract Co-Author: Nothing to Disclose

Amanda Klaas, Abstract Co-Author: Nothing to Disclose

Deborah Sultan, Abstract Co-Author: Nothing to Disclose

AIXIAO LI, Abstract Co-Author: Nothing to Disclose

Liya Yuan MD, Abstract Co-Author: Nothing to Disclose

Efrem Mebrahtu, Abstract Co-Author: Nothing to Disclose

Keith M. Rich MD, Abstract Co-Author: Nothing to Disclose

Jonathan Edward McConathy MD, PhD, Abstract Co-Author: Speakers Bureau, Eli Lilly and Company Research Consultant, Eli Lilly and Company Research Consultant, General Electric Company Research Consultant, Blue Earth Diagnostics Ltd Research Consultant, Siemens AG

Suzanne Elizabeth Lapi PhD, Abstract Co-Author: Nothing to Disclose

Many cancers show an upregulation of nutrient transport including amino acid transporters to meet their altered metabolism. System A amino acid transporters are capable of concentrating substrates within cells which can provide higher tumor to background ratios and prolonged retention in tumors which are desirable properties for oncologic imaging agents. The purpose of this work is to exploit these properties of system A transport by synthesizing and radiolabeling the novel 76Br derivative of bromo vinyl amino isobutyric acid (BrVAIB), an analogue of the known radioiodinated (123/131I) system A tracer, IVAIB. The longer half-life of 76Br (16.2 hr) and positron emission makes this radionuclide of interest for long distance distribution and imaging at later time points.

Starting with enantiopure N-boc-α-methyl-L-serine, the vinyl-trimethyl tin precursor needed for labeling, was synthesized in 4 steps. Radiobromination was carried out using peracetic acid and [76Br]NH4Br in water. The labeled compound was fully deprotected and isolated using ion-retardation resin in series with a C-18 sep pak cartridge. Compound purity and identity was verified using iTLC and radioHPLC. [76Br]BrVAIB was injected i.v. into mice with subcutaneous DBT tumors for biodistribution (5 time points, n = 4) and into mice with intracranial gliomas (n = 4) for small animal PET studies. 

[76Br]BrVAIB was readily labeled and isolated in a 55% yield (> 99% purity). Biodistribution studies showed average maximal tumor uptake between 30 min and an hour, post-injection, at 3.8 + 0.9 and 3.7 + 0.4 %ID/gram, respectively. After 3 hours, BrVAIB had cleared most other measured organs, with the tumor still retaining 1.6 + 0.4 %ID/gram. PET images clearly show uptake in the right, frontal region of the brain in 3 of the mice at 3 hr p.i. and can still be seen at 24 hr.   

(S)-[76Br]BrVAIB can easily be synthesized and radiolabeled in good yields and shows modest uptake and retention in intracranial DBT glioma tumors. Future work will include evaluation of the N-methyl amino analogue of BrVAIB which may have more selectivity for system A transporters and prolonged retention in tumors.

A 76Br-labeled amino acid will provide a longer-lived alternative to 11C- and 18F-labeled system A tracers, facilitating distribution to remote sites for imaging at later time points post injection.

Burkemper, J, Huang, C, Klaas, A, Sultan, D, LI, A, Yuan, L, Mebrahtu, E, Rich, K, McConathy, J, Lapi, S, Radiolabeling and Biological Evaluation of a Novel 76Br-labeled Amino Acid, BrVAIB, for PET Imaging of Brain Tumors.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14007920.html