PT  - JOURNAL ARTICLE
AU  - Colovic, Milena
AU  - Yang, Hua
AU  - Southcott, Lily
AU  - Merkens, Helen
AU  - Colpo, Nadine
AU  - Bénard, Francois
AU  - Schaffer, Paul
TI  - Comparative Evaluation of [<sup>18</sup>F]5-Fluoroaminosuberic Acid and (4<em>S</em>)-4-3-[<sup>18</sup>F]fluoropropyl)-<span class="sc">l</span>-Glutamate as System <span class="inline-formula" id="inline-formula-1"><img src="pending:yes" l:ref-type="journal" hwp:journal="jnumed" hwp:article="jnumed.122.265254" l:sub-ref="mml-math-1" l:type="image/*" class="math mml" alt="Formula"/></span>–Targeting Radiopharmaceuticals
AID  - 10.2967/jnumed.122.265254
DP  - 2023 Apr 27
TA  - Journal of Nuclear Medicine
PG  - jnumed.122.265254
4099  - http://jnm.snmjournals.org/content/early/2023/04/27/jnumed.122.265254.short
4100  - http://jnm.snmjournals.org/content/early/2023/04/27/jnumed.122.265254.full
AB  - System is an appealing biomarker for targeting oxidative stress with oncologic PET imaging and can serve as an alternative PET biomarker to other metabolic indicators. In this paper, we report a direct comparison of 2 18F-labeled amino acid radiopharmaceuticals targeting system , [18F]5-fluoroaminosuberic acid ([18F]FASu) and (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG), in terms of their uptake specificity and ability to image glioma and lung cancer xenografts in vivo. Methods: Both tracers were synthesized according to previously published procedures. In vitro uptake specificity assays were conducted using prostate (PC-3), glioblastoma (U-87), colorectal (HT-29), ovarian (SKOV3), breast (MDA-MB-231), and lung cancer (A549) cell lines. PET/CT imaging and biodistribution studies were conducted in immunocompromised mice bearing U-87 or A549 xenografts. Results: In vitro cell uptake assays showed that the tracers accumulated in cancer cells in a time-dependent manner and that the uptake of [18F]FASu was blocked by the system inhibitor sulfasalazine and rose bengal, but not by system L inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, system inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid, or l-serine, which is a substrate for transporter systems A, ACS, B0, and B0,+. Conversely, [18F]FSPG uptake decreased significantly in the presence of an excess of L-trans-pyrrolidine-2,4-dicarboxylic acid in 2 of 3 tested cell lines, indicating some reliance on system in these cells. In an in vivo setting, [18F]FASu and [18F]FSPG generated good-contrast PET images in U-87 and A549 tumor–bearing mice. Tracer accumulation in A549 tumors was 5.0 ± 0.8 percentage injected dose (%ID)/g ([18F]FASu, n ≥ 5) and 6.3 ± 1.3 %ID/g ([18F]FSPG, n ≥ 6, P = 0.7786), whereas U-87 xenografts demonstrated uptake of 6.1 ± 2.4 %ID/g ([18F]FASu, n ≥ 4) and 11.2 ± 4.1 %ID/g ([18F]FSPG, n ≥ 4, P = 0.0321) at 1 h after injection. Conclusion: [18F]FSPG had greater in vitro uptake than [18F]FASu in all cell lines tested; however, our results indicate that residual uptake differences exist between [18F]FSPG and [18F]FASu, suggesting alternative transporter activity in the cell lines tested. In vivo studies demonstrated the ability of both [18F]FASu and [18F]FSPG to image glioblastoma (U-87) and non–small cell lung cancer (A549) xenografts.