Abstract
Sigma-1 receptors (Sig1R) are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET) can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S)-(−)- and (R)-(+)-[18F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously) implanted tumors. Therefore, a brain tumor model (U87-MG) with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [18F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB).
Highlights
In clinical oncology, major efforts are dedicated to the optimization of cancer treatment either with chemotherapeutics or radiation therapy [1]
Starting from the cellular level, we investigated the Sigma-1 receptors (Sig1R) synthesis with Western blot and the accumulation of (S)-(−)- and (R)-(+)-[18 F]fluspidine in the human prostatic cancer cells DU145 and PC3, as well as in the cell lines A431 and FaDu, A375, and U87-MG
The Sig1R expression was analyzed in lysates from melanoma (A375), squamous cell/epidermoid carcinoma
Summary
Major efforts are dedicated to the optimization of cancer treatment either with chemotherapeutics or radiation therapy [1]. Molecules 2018, 23, 702 applied radiotracers for that purpose is the glucose analog [18 F]fluorodeoxyglucose ([18 F]FDG) which accumulates in tissues with high metabolic activity [2,3]. It has shown some limitations in the detection of tumors like prostatic carcinoma DU145 [4] or PC-3 xenografts [5], A431 xenografts [6], FaDu tumors [7], A375 tumors [8], and in U87-MG glioblastoma [9,10]. For brain tumors, the high background uptake of glucose in healthy brain makes the detection of small or low-grade tumors almost impossible [15]
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