The present disclosure encompasses embodiments of nucleic acid minicircle vectors most advantageous for the detection of tumor cells. In particular, the minicircles of the disclosure incorporate a tumor-specific promoter operably linked to a nucleotide sequence desired to be selectively expressed in a tumor cell or a tissue comprising a population of tumor cells. In embodiments of the disclosure, the minicircle vectors comprise a tumor-specific promoter operably linked to a nucleotide sequence encoding a polypeptide useful as a reporter. Accordingly, when expressed by a recipient tumor cell, the reporter may be detectable, thereby providing information such as a visual image of the tumor cell and/or its location in a tissue of the subject human or non-human animal. Tumor-specific minicircle vectors driving the expression of either secreted embryonic alkaline phosphatase or firefly luciferase and their utility validated for detecting tumors after systemic administration using blood- and/or imaging-based assays are disclosed.