Objective:

To appropriately extend the in vivo circulation time of ginsenoside-like prostate-specific membrane antigen (PSMA) targeting probes and develop a novel

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Ga-labeled diagnostic probe for prostate cancer.

Methods:

The ligand P214 (using p-SCN-Bn-DOTA as a bifunctional chelator) was synthesized using solid-phase synthesis

and its affinity was measured. The ligand was added to a buffer containing

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Ga

3+

ions

reacted at 95 ℃ for 5 min

and then purified. The radiochemical purity was determined using radioactive thin-layer chromatography. The in vitro stability

lipophilicity and human serum protein binding rate of

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Ga-P214 were evaluated

followed by cell uptake experiments.

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Ga-P214 was injected into 22Rv1 tumor-bearing mice

and micro-positron emission tomography (PET)/computed tomography (CT) imaging was performed at specific time points

with comparative imaging using

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Ga-P137. Mice were sacrificed at 30

60 and 120 min post-injection via tail vein

and organs of interest were weighed

counted

and the percentage of injected dose per gram of tissue (%ID/g) was calculated.

Results:

The target ligand P214 was successfully synthesized with a K i value of 0.085 nmol/L

and the radiochemical purity exceeded 95%. The labeled product

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Ga-P214 remained stable in saline and 37 ℃ mouse serum for 2 h. The lipophilicity (partition coefficient) of

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Ga-P214 was -3.17±0.09

and the human serum albumin binding rate was (88.86±0.51)%

significantly higher than that of

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Ga-P137 (74.01±1.17)%. Cell experiments demonstrated that

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Ga-P214 was effectively taken up by PSMA+cells (22Rv1)

with uptake rates of (0.39±0.14)

(0.55±0.09)

and (0.54±0.12) %ID/10 5 cells at 30

60

and 120 min of incubation

respectively

which could be inhibited by the PSMA inhibitor ZJ43. At 60 min post-injection

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Ga-P214 had a higher maximum standard uptake value (SUV

max

) in the tumor region (1.40±0.11

vs

0.80±0.04)

which increased over time. Biodistribution in tumor-bearing mice showed that

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Ga-P214 had significantly higher uptake in tumors compared to

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Ga-P137 ［(44.15±6.25)%ID/g

vs

(19.76±3.56)%ID/g at 120 min post-injection］

with superior tumor/muscle

tumor/blood

and tumor/liver ratios (127.63

33.87

and 12.68

respectively).

Conclusion:

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Ga-P214 exhibits ideal biodistribution

appropriately extends the in vivo circulation time of ginsenoside-like probes

and significantly increases uptake in PSMA-positive tumors

making it a promising candidate for prostate cancer diagnosis with considerable potential to be developed into a therapeutic probe.