Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours

Objective The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo . Methods [ 68 Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([ 68 Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [ 68 Ga] Ga 3+ . The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [ 68 Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM 3 xenograft-bearing nude mice were studied in vitro and in vivo . Results [ 68 Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was −2.53 ± 0.19. The tracer displayed excellent stability in vitro . 68 Ga–MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [ 68 Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [ 68 Ga]Ga-MALAT-1-ASO can target tumours in vivo . Conclusions We conclude that [ 68 Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [ 68 Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.