Molecular imaging of the kidneys

Abstract

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive, and accurate diagnosis. The most recent imaging technology, positron emission tomography, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H(2)(15)O, (82)RbCl, and [(64)Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype angiotensin subtype 1 receptor by the use of in vivo positron emission tomography. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc99m MAG3 as well as some novel radiopharmaceuticals, such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands, have been used for molecular renal imaging. In addition, other radioligands that interact with the organic cation transporters or peptide transporters have been developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule 1, which is highly expressed in kidney injury and renal cancer but not in normal kidneys. Although pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on up-regulated molecules in response to tissue stress resulting from obstruction will be of great implication. Monocyte chemoattractant protein-1 is a well-suited molecule here. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [(18)F] fluorodeoxyglucose, other radioligands, such as [(11)C] acetate and anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid, have emerged. Radioimmunoimaging with [(124)I] G250 could lead to radioimmunotherapy for renal cancer. Considering the increasing age of general population, the incidence of kidney diseases, such as atherosclerosis, diabetic nephropathy, and cancer, is expected to increase. Successful management of these diseases offers an opportunity and a challenge for development of novel molecular imaging technologies.

Figure 1

PET images obtained with C-11 KR 31173, a radioligand that selectively binds to the AT1R. Early images obtained at 2 min post injection show symmetrical uptake in a control pig (A) with symmetrical retention at 30 min (B). On the other hand, reduced uptake is noted in the right kidney with renal artery stenosis (C) followed by significant radioligand retention (D). (Reprinted with permission from Wolters Kluwer Health (16)).

Figure 2

Autoradiography of the angiotensin subtype 1 receptor (AT1R). Compared to the control (left) there is significant upregulation of the receptor in the cortical glomeruli (red dots) and the medullary tubular epithelium (red area) of the hypoperfused kidney (right). (Reprinted with permission from Wolters Kluwer Health (16)).

Figure 3

Membrane proteins in the proximal tubular epithelium involved in the transport of organic anions (OAT) and cations (OCT). PAH=paraaminohippuric acid. MRP2=multidrug resistance protein 2.

Figure 4

Urinary MCP-1 and its correlation with renal kinetics of [^99mTc]MAG3. Urinary MCP-1 is significantly increased in patients with UPJ obstruction (A) and shows positive correlation with the mean cortical time of transit (MTT), r = 0.565, P< 0.03 (B); and negative correlation with [^99mTc]MAG3 clearance, r = 0.769, P < 0.01 (C). (Reprinted with permission from the Nature Publishing Group (43)).

Figure 5

Incidentally detected renal cancer of the right kidney in a patient who received a [¹⁸F]FDG PET /CT-scan (A and B) for postoperative staging of right upper lobe lung cancer. Noncontrast CT (A) and PET (B) images show residual disease in the right hilum and a small exophytic isometabolic lesion on the upper pole of the right kidney that is hypervascular on contrast CT (C) and suspicious for renal carcinoma.

Figure 6

PET/CT imaging (A, B) with [¹²⁴I]G250 shows high accumulation in clear cell renal carcinoma confirmed by ex vivo autoradiography (Reprinted with permission from the Nature Publishing Group (61)).

Figure 7

Whole body PET scan with Na¹⁸F in a patient with metastatic renal carcinoma. The image quality is excellent with high bone to soft tissue ratio in healthy bones and intense tracer accumulation in metastatic lesions. (Reprinted with permission from Wolters Kluwer Health (67)).