Preclinical evaluation of ⁶⁸Ga-pentixafor for PET imaging of CXCR4 expression in lymphoproliferative diseases and solid tumors: a comparison to ¹⁸F-FDG PET imaging

Background: Chemokine receptor CXCR4 has been described to play a pivotal role in tumor growth and progression, tumor invasiveness and metastasis. Overexpression of the receptor has been reported in many kinds of tumors. The expression of chemokine receptor is a predictor of survival. Thus CXCR4 may serve as a promising new target for both diagnostic and therapeutic interventions, especially in selecting candidates for peptide receptor radionuclide therapy based on CXCR4. Our research is to assess the presentation of a new CXCR4-ligand (⁶⁸Ga-pentixafor) in mice bearing daudi,opm-2,panc1 and H69 cell line xenografts for lymphoma, multiple myeloma(MM) ,pancreatic cancer and small cell lung cancer (SCLC)respectively and compare the results with ¹⁸F-FDG PET imaging. Method The synthesis of ⁶⁸Ga-pentixafor was performed as described in published articles. After purification via Sep Pak Plus Light C18 cartridge, the ethanolic product fraction was diluted with PBS and used as such for the experiments. For PET studies, an average of 15.2 MBq ⁶⁸Ga-pentixafor and FDG was injected intravenously into the tail vein of isofluorane anesthesized female daudi(n=4),opm-2(n=4),panc1(n=4) and H69(n=4)-bearing SCID mice in different day. Static PET imaging was acquired at 30,60,90,120mins p.i. (Simens microPET scanner).Animal studies were approved by the Ethics Committee from our institutional.

Results: 1. In small-animal PET imaging studies for lymphoma, the uptake of ⁶⁸Ga-pentixafor in the daudi xenografts was clearly delineated 120mins p.i. (%ID/g of tumor :30min1.46±0.81;60min1.85±0.70; 90mim1.77± 0.67;120min2.50±0.47) (A). The tumor accumulation was higher than the activity uptake in background tissues except for the major excretory organs, leading to excellent tumor/background ratios which maintained in 120mins p.i..And the tumor/ muscle ratio was significantly higher than those of ¹⁸F-FDG imaging(Table1). 2. The same results were also observed in the ⁶⁸Ga-pentixafor PET for MM. The opm2 xenografts was most clearly depicted 120mins p.i. (%ID/g of tumor :30min3.63±1.52;60min4.05±2.02;90mim5.00±2.77;120min5.33±3.09)(B).The tumor/background ratios was especially high in tumor/muscle and tumor/liver which were both much more higher than those of ¹⁸F-FDG PET imaging(Table1). 3. The panc-1 xenografts of pancreatic cancer showed slightly uptake on ⁶⁸Ga-pentixafor PET (%ID/g of tumor :30min0.46±0.12;60min0.37± 0.14 ;90min0.36±0.06;120min0.41±0.14) which was lower than those of ¹⁸F-FDG PET(%ID/g of tumor :30min1.40±1.18; 60min1.50±1.30; 90min1.40±1.28; 120min1.50±1.35). But the tumor/background ratio of ⁶⁸Ga-pentixafor PET was higher than those of ¹⁸F-FDG PET imaging except for the major excretory organs(Table1). 4. For SCLC, the uptake of ⁶⁸Ga-pentixafor in the H69 xenografts was clearly delineated 30mins p.i.(%ID/g of tumor:30min 7.70±1.46;60min 4.43±0.84;120min3.47±0.15).And the tumor accumulation to background tissues (Tumor/Muscle:30min5.86±1.03;60min9.27±2.31; 120min12.55±2.72)was also higher comparing to those of FDG imaging and this excellent ratio maintained in 120mins p.i..

Conclusions: ⁶⁸Ga-pentixafor is a suitable tracer for targeting and imaging of CXCR4 receptor expression in vivo of lymphoma, MM and SCLC which enables the further evaluation of this new tracer in human studies. The imaging for pancreatic cancer needs further investigation.

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