In Vivo Quantitative Whole-Body Perfusion Imaging Using Radiolabeled Copper(II) Bis(Thiosemicarbazone) Complexes and Positron Emission Tomography (PET)

The development of methods for production of a radiotracer for use in human studies with positron emission tomography (PET) is often a time-consuming process of optimizing radiolabelling yields and handling procedures. Sometimes the radiotracer is not the original drug, but rather a derivative with unknown in vivo pharmacological properties. We have developed a fast and simple method of testing putative new PET tracers in vivo in small animals. The procedure has been validated in rats with different PET tracers with known kinetic and pharmacological properties ([2-18F]2-fluoro-2-deoxy-d-glucose, [ N-methyl-11C]Ro 15-1788, and [15O]butanol). The tracer concentration in arterial blood was continuously measured to obtain the brain input function. Following image reconstruction of the scans, time–activity curves of selected regions of interest were generated. Estimations of CMRglc (1.0 ± 0.2 μmol g−1 min−1), CBF (1.4 ± 0.4 ml g−1 min−1) and transport rate constants for [ N-methyl-11C]Ro 15-1788 (K1 = 0.44 ± 0.01 ml g−1 min−1 and k2 = 0.099 ± 0.005 min−1) as well as calculated first pass extraction (0.32 ±0.1) are in reasonable agreement with literature values. Small animal studies require minimal amounts of radioactivity and can be performed without sterility and toxicology tests. They may serve as a preliminary basis for radiation safety calculations because whole body scans can be performed even with a head scanner. The major advantage of this procedure in comparison to ex vivo autoradiography is that very few experiments are necessary to reliably determine the properties of the blood–brain barrier transport of the radiotracer and the possible whole brain receptor binding characteristics.

Download Full-text

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

Journal of Clinical Medicine ◽

10.3390/jcm10061151 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1151

Author(s):

Ruth González-Gómez ◽

Roberto A. Pazo-Cid ◽

Luis Sarría ◽

Miguel Ángel Morcillo ◽

Alberto J. Schuhmacher

Keyword(s):

Positron Emission Tomography ◽

Pancreatic Ductal Adenocarcinoma ◽

Imaging Techniques ◽

Metastatic Tumor ◽

Emission Tomography ◽

Whole Body ◽

Ductal Adenocarcinoma ◽

Non Invasive ◽

Positron Emission

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”.

Download Full-text

CellGPS: Whole-body tracking of single cells by positron emission tomography

10.1101/745224 ◽

2019 ◽

Author(s):

Kyung Oh Jung ◽

Tae Jin Kim ◽

Jung Ho Yu ◽

Siyeon Rhee ◽

Wei Zhao ◽

...

Keyword(s):

Positron Emission Tomography ◽

Single Cells ◽

The Body ◽

Emission Tomography ◽

Whole Body ◽

Cell Trafficking ◽

Anatomical Landmarks ◽

Average Cell ◽

Positron Emission

AbstractIn vivo molecular imaging tools are critically important for determining the role played by cell trafficking in biological processes and cellular therapies. However, existing tools measure average cell behavior and not the kinetics and migration routes of individual cells inside the body. Furthermore, efflux and non-specific accumulation of contrast agents are confounding factors, leading to inaccurate estimation of cell distribution in vivo. In view of these challenges, we report the development of a “cellular GPS” capable of tracking single cells inside living subjects with exquisite sensitivity. We use mesoporous silica nanoparticles (MSN) to concentrate 68Ga radioisotope into live cells and inject these cells into live mice. From the pattern of annihilation photons detected by positron emission tomography (PET), we infer, in real time, the position of individual cells with respect to anatomical landmarks derived from X-ray computed tomography (CT). To demonstrate this technique, a single human breast cancer cell was tracked in a mouse model of experimental metastasis. The cell arrested in the lungs 2-3 seconds after tail-vein injection. Its average velocity was estimated at around 50 mm/s, consistent with blood flow rate. Other cells were tracked after injection through other routes, but no motion was detected within 10 min of acquisition. Single-cell tracking could be applied to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy, or the distribution of cells after transplantation in regenerative medicine.

Download Full-text