Imaging tumors in their early stages is crucial to increase the surviving rate of cancer patients. Currently most fluorescence probes visualize the neoplasia by targeting the tumor‐associated receptor over‐expressed on the cancer cell membrane. However, the expression level of these receptors in vivo is hard to predict, which limits their clinical translation. Furthermore, the signal output of these receptor‐targeting probes usually stays at a high level, which leads to a strong background signal in normal tissue due to non‐specific binding. In contrast to receptors, characteristics of the tumor microenvironment – such as acidosis – are pervasive in almost all solid tumors and can be easily accessed. In this work, a novel biodegradable nanoprobe InNP1 that demonstrates pH‐activated near‐infrared (NIR) fluorescence in both human glioblastoma U87MG cancer cells in vitro and the subcutaneous U87MG tumor xenografts in vivo is developed. Bio‐distribution, in vivo optical imaging, and autoradiography studies demonstrate that the pH‐activated NIR fluorescence is the dominant factor responsible for the high tumor/normal tissue (T/N) ratio of InNP1 in vivo. Overall, the work provides a nanoprobe prototype to visualize the solid tumor in vivo with high sensitivity and minimal systemic toxicity by sensing the tumor acidic microenvironment.
Currently,
positron emission tomography/computed tomography (PET/CT)
is an important method for the discovery and diagnosis of digestive
system tumors. However, the shortage of specific imaging tracer limits
the effectiveness of PET. Triggering receptor expressed on myeloid
cells 2 (TREM2) as an M2-type macrophage biomarker is receiving much
attention considering its high abundance and specificity, which could
be an ideal target for PET imaging. First, the expression of TREM2
in tumors and corresponding normal tissues was analyzed using a database
and was verified by tissue microarrays and murine model slices, and
we found that the expression of TREM2 in tumor tissues was significantly
higher than that in normal tissues and enteritis tissues. Then, we
established a macrophage co-culture system to obtain tumor-associated
macrophages (TAMs). Compared with M1-type macrophages and tumor cells,
TAMs had a higher expression level of TREM2. The novel radioligand 68Ga-NOTA-COG1410 was successfully synthesized for TREM2 targeting
PET imaging. The biodistribution and micro-PET/CT results showed high
uptake of 68Ga-NOTA-COG1410 in the tumor but not in areas
of inflammation. The data testified that 68Ga-NOTA-COG1410
was a specific radioligand targeting TREM2, which could be used to
distinguish tumors from inflammation. Using 68Ga-NOTA-COG1410,
the effectiveness of PET on digestive tumors imaging may be enhanced.
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