5-Carboxy-fluorescein-labeled octreotate

Excerpt

Octreotate labeled with 5-carboxy-fluorescein, abbreviated as OcF, is an optical imaging agent developed by Fottner et al. for in vivo imaging of somatostatin receptors (SSTRs) in neuroendocrine tumors with miniaturized confocal laser-scanning microscopy (CLM) (1). SSTRs are highly expressed in neuroendocrine tumors (2, 3). The excitation and emission wavelengths of 5-carboxy-fluorescein are 492 nm and 518 nm, respectively. The molecular weight of octreotate is 1033.3.

CLM is an emerging technique that integrates the miniaturized components of a confocal laser scanner into the tip of a conventional endoscope (4-7). During imaging, a solid laser delivers an excitation wavelength of 488 nm on the surface of target organs, and light emission is detected at 505–585 nm. Serial images are collected at a scan rate of 0.8 frames/s at 1024 × 1024 pixels or 1.6 frames/s at 1024 × 512 pixels. The laser power output can be adjusted from 0 µW to 1000 µW to achieve appropriate tissue contrast. The optical slice thickness is usually 7 μm, with a lateral resolution of 0.7 μm and an imaging plane depth to 250 μm from the tissue surface. Tissue images are produced on the basis of different refractive indices from biological tissues, and image contrast is enhanced with application of contrast agents such as intravenous sodium fluorescein or topical acriflavine (7, 8). Virtual histology can be created with CLM, which allows visualization of pathological changes at cellular and subcellular levels in addition to standard videoendoscopy (5, 7). Studies with CLM have demonstrated its effectiveness in screening inflammatory and early malignant diseases of the gastrointestinal tract (1). However, the CLM technique does not allow clear, simultaneous, in vivo imaging of the tissue anatomy together with a dynamic visualization of molecular targets like the SSTRs (1).

Fottner et al. developed a miniaturized CLM technique that allows the specific molecular imaging of SSTRs in vivo and in real time (1). For selective visualization of SSTRs, a contrast agent for CLM was specifically synthesized by conjugating 5-carboxy-fluorescein to octreotate (referred to as OcF). With the miniaturized CLM and OcF, equal morphological resolution of SSTR-expressing cell structures (pancreatic islet cells, renal tubular cells, and neuroendocrine tumors) was achieved, unlike with standard histological tissue investigation. Fottner et al. concluded that the CLM technique together with OcF allows specific visualization of SSTR-expressing neuroendocrine tumor cells, while expression of SSTRs and SSTR-mediated endocytosis of somatostatin and its analogs in neuroendocrine tumors represent the molecular basis for various clinical diagnostic and therapeutic applications (1).