Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 +/- 0.9 x 10(-3) % of injected dose (ID)/g] than in the control group (3.6 +/- 1.2 x 10(-3) %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 +/- 2.8 vs. 9.8 +/- 1.7 x 10(-3) %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.

Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.

Pancreatic diseases, chronic pancreatitis, pancreatic cancer and diabetes mellitus, taken together, occur in >10% of the world population. Pancreatic diseases, as with other diseases, benefit from early intervention and appropriate diagnosis. Although imaging technologies have given clinicians an unprecedented toolbox to aid in clinical decision-making, advances in these technologies and development of molecular-based diagnostic tools could enable physicians to identify diseases at an even earlier stage and, thereby, improve patient outcomes. In this Review, we discuss and identify gaps in the use of imaging techniques for the early detection and appropriate treatment stratification of various pancreatic diseases, including diabetes mellitus, acute and chronic pancreatitis and pancreatic cancer. Imaging techniques discussed are MRI, CT, PET and ultrasonography. Additionally, the identification of new molecular targets for imaging and the development of contrast agents that are able to give molecular information in noninvasive radionuclear imaging and ultrasonography are emerging areas of innovation that could lead to increased diagnostic accuracy and improved patient outcomes.

(99m)Tc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.

The development of novel molecular cancer imaging agents has considerably advanced in recent years. Numerous cancer imaging agents have demonstrated remarkable potential for aiding the diagnosis, staging, and treatment planning at the preclinical stage which in turn has led to a number of agents being approved for human trials. Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly common carcinoma with an overall 5-year survival rate of about 6%. As detection technologies progress, the need for molecular imaging tools that will allow the diagnosis at an early stage will be crucial to improving patient outcomes. In this review, we will highlight agents that illuminate various cell populations that comprise the tumor: epithelial, endothelial, and stromal tumor cells.

Vascular cell adhesion molecule 1 (VCAM-1) plays a major role in the chronic inflammatory processes involved in vulnerable atherosclerotic plaque development. We previously showed that the 99m Tc-labeled major histocompatibility complex 1-derived peptide B2702p bound specifically to VCAM-1 and allowed the ex vivo imaging of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits. However, B2702p target-to-background ratio was suboptimal for the in vivo imaging of VCAM-1 expression in atherosclerotic lesions. To improve the target-to-background ratio, 20 derivatives of B2702p (B2702p1-B2702p20) were synthesized using the alanine scan methodology. We hypothesized that 99m Tc-radiolabeled B2702p derivatives might allow the molecular imaging of VCAM-1 expression in an experimental model of atherosclerosis. Methods: A mouse model of focal atherosclerotic plaque development induced by left carotid artery ligation in apolipoprotein E double-knockout (ApoE 2/2 ) mice was used (n 5 82). 99m Tc-B2702p and 99m Tc-B2702p1-99m Tc-B2702p20 were injected intravenously in anesthetized animals 3 wk after the ligation. Whole-body planar imaging was performed for 3 h. SPECT imaging of 6 additional ligated ApoE 2/2 mice was also performed with 99m Tc-B2702p1. The animals were then euthanized, and the biodistribution of 99m Tc-labeled peptides was evaluated by g-well counting of excised organs. Expression of VCAM-1 in the ligated and contralateral carotid arteries was evaluated by immunohistology. Results: Robust VCAM-1 immunostaining was observed in the left carotid atherosclerotic lesions as a consequence of artery ligation, whereas no VCAM-1 expression was detected in the contralateral carotid artery. Among all evaluated peptides, 99m Tc-B2702p1 exhibited the most favorable properties. By g-well counting, there was a significant 2.0-fold increase in the 99m Tc-B2702p1 left-to-right carotid artery activity ratio (2.6 6 0.6) and a 3.4-fold increase in the left carotid-to-blood activity ratio (1.4 6 0.4) in comparison to 99m Tc-B2702p (1.3 6 0.2 and 0.4 6 0.1, respectively, P , 0.05 for both comparisons). Similarly, planar image quantification indicated a higher left-to-right carotid activity ratio in 99m Tc-B2702p1-than in 99m Tc-B2702p-injected mice (1.2 6 0.1 vs. 1.0 6 0.0, respectively, P , 0.05). Finally, a significantly higher 99m Tc-B2702p1 activity in the left than in the right carotid artery was observed by SPECT imaging (2.2 6 0.4 vs. 1.4 6 0.3 cpm/mm 2 / injected dose, respectively, P , 0.05). Conclusion: 99m Tc-B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Despite major advances in the treatment of CVD, a high proportion of CVD victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerotic plaques in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could allow the identification of vulnerable patients by non-invasive in vivo scintigraphic imaging following administration of a radiolabeled tracer. The purpose of this review is to provide an overview of radiotracers that have been recently evaluated for the detection of vulnerable plaques together with the biological rationale that initiated their development. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable plaques in carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of coronary arteries remains challenging, mostly because of their small size and their vicinity with unbound circulating tracer. The experimental and pilot clinical studies reviewed in the present paper represent a fundamental step prior to the evaluation of the efficacy of any selected tracer for the early, non-invasive detection of vulnerable patients.

Imaging holds an important role in the diagnosis of lung diseases. Along with clinical tests, noninvasive imaging techniques provide complementary and valuable information that enables a complete differential diagnosis. Various novel molecular imaging tools are currently under investigation aimed toward achieving a better understanding of lung disease physiopathology as well as early detection and accurate diagnosis leading to targeted treatment. Recent research on molecular imaging methods that may permit differentiation of the cellular and molecular components of pulmonary disease and monitoring of immune activation are detailed in this review. The application of molecular imaging to lung disease is currently in its early stage, especially compared to other organs or tissues, but future studies will undoubtedly reveal useful pulmonary imaging probes and imaging modalities.