RT Journal Article
SR Electronic
T1 Preclinical Comparison of the <sup>64</sup>Cu- and <sup>68</sup>Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [<sup>68</sup>Ga]Ga-AMTG PET/CT
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1654
OP 1659
DO 10.2967/jnumed.123.265771
VO 64
IS 10
A1 Koller, Lena
A1 Joksch, Markus
A1 Schwarzenböck, Sarah
A1 Kurth, Jens
A1 Heuschkel, Martin
A1 Holzleitner, Nadine
A1 Beck, Roswitha
A1 von Amsberg, Gunhild
A1 Wester, Hans-Jürgen
A1 Krause, Bernd Joachim
A1 Günther, Thomas
YR 2023
UL http://jnm.snmjournals.org/content/64/10/1654.abstract
AB Despite the recent success of prostate-specific membrane antigen (PSMA)–targeted compounds for theranostic use in prostate cancer (PCa), alternative options for the detection and treatment of PSMA-negative lesions are needed. We have recently developed a novel gastrin-releasing peptide receptor (GRPR) ligand with improved metabolic stability, which might improve diagnostic and therapeutic efficacy and could be valuable for PSMA-negative PCa patients. Our aim was to examine its suitability for theranostic use. We performed a comparative preclinical study on [64Cu]Cu-/[68Ga]Ga-AMTG ([64Cu]Cu-/[68Ga]Ga-α-Me-l-Trp8-RM2) using [64Cu]Cu-/[68Ga]Ga-RM2 ([64Cu]Cu-/[68Ga]Ga-DOTA-Pip5-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) as a reference compound and investigated [68Ga]Ga-AMTG in a proof-of-concept study in a PCa patient. Methods: Peptides were labeled with 64Cu (80 °C, 1.0 M NaOAc, pH 5.50) and 68Ga (90 °C, 0.25 M NaOAc, pH 4.50). GRPR affinity (half-maximal inhibitory concentration, room temperature, 2 h) and GRPR-mediated internalization (37 °C, 60 min) were examined on PC-3 cells. Biodistribution studies were performed at 1 h after injection in PC-3 tumor–bearing mice. For a first-in-humans application, 173 MBq of [68Ga]Ga-AMTG were administered intravenously and whole-body PET/CT scans were acquired at 75 min after injection. Results: 64Cu- and 68Ga-labeling proceeded almost quantitatively (&gt;98%). All compounds revealed similarly high GRPR affinity (half-maximal inhibitory concentration, 1.5–4.0 nM) and high receptor-bound fractions (79%–84% of cell-associated activity). In vivo, high activity levels (percentage injected dose per gram) were found in the PC-3 tumor (14.1–15.1 %ID/g) and the pancreas (12.6–30.7 %ID/g), whereas further off-target accumulation was low at 1 h after injection, except for elevated liver uptake observed for both 64Cu-labeled compounds. Overall biodistribution profiles and tumor-to-background ratios were comparable but slightly enhanced for the 68Ga-labeled analogs in most organs. [68Ga]Ga-AMTG confirmed the favorable pharmacokinetics—as evident from preclinical studies—in a patient with metastasized castration-resistant PCa showing intense uptake in several lesions. Conclusion: AMTG is eligible for theranostic use, as labeling with 64Cu and 68Ga, as well as 177Lu (known from previous study), does not have a negative influence on its favorable biodistribution pattern. For this reason, further clinical evaluation is warranted.