No abstract

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance ...

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.