Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.

Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation.

Ac-MACROPATATE: A Novel α-Particle Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in treatment for metastatic and locoregional disease. Peptide receptor radionuclide therapy with Lu-DOTATATE (DOTA-octreotate), a β-particle-emitting somatostatin derivative, has demonstrated survival benefit in patients with SSTR-positive NETs.

Cell radiolabeling with acoustophoresis cell washing.

Labeling immune cells with zirconium-89 (Zr)-oxine has become a viable method to track cells in vivo by PET in various pre-clinical animal models and in clinical applications. Currently, Zr-oxine cell labeling is performed manually, which requires a highly trained specialist and is prone to human error. As the first phase in developing a fully automated radiolabeling system to address this problem, we assess the use of acoustophoresis cell washing to replace the centrifugal cell washing used in the current Zr-oxine cell radiolabeling procedure.

Advances in Preclinical PET.

The classical intent of PET imaging is to obtain the most accurate estimate of the amount of positron-emitting radiotracer in the smallest possible volume element located anywhere in the imaging subject at any time using the least amount of radioactivity. Reaching this goal, however, is confounded by an enormous array of interlinked technical issues that limit imaging system performance. As a result, advances in PET, human or animal, are the result of cumulative innovations across each of the component elements of PET, from data acquisition to image analysis.

Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma.

Molecular imaging approaches for metabolic and physiologic imaging of tumors have become important for treatment planning and response monitoring. However, the relationship between the physiologic and metabolic aspects of tumors is not fully understood. Here, we developed new hyperpolarized MRI and electron paramagnetic resonance imaging procedures that allow more direct assessment of tumor glycolysis and oxygenation status quantitatively.

Tracking of Adoptively Transferred Natural Killer Cells in Rhesus Macaques Using Zirconium-Oxine Cell Labeling and PET Imaging.

Purpose: Trials of adoptive natural killer (NK)-cell immunotherapy for hematologic malignancies have thus far shown only marginal effects, despite the potent antitumor activity of these cells. Homing of infused cells to tumor microenvironments is critical for efficacy, but has not been well characterized. We established a novel method to track and quantify the distribution of adoptively transferred NK cells using rhesus macaques (RM) as a clinically relevant preclinical model.

The Distribution Volume of F-Albumin as a Potential Biomarker of Antiangiogenic Treatment Efficacy.

F-albumin, a vascular imaging agent, may have potential to assess tumor responses to anti-angiogenic therapies. In these studies tumor distribution volume of F-albumin were first determined in various human tumor xenografts from biodistribtuion measurments and then one of the tumor type was used to evaluate changes in F-albumin uptake in anti-angiognic tumor model. F-albumin was synthesized via conjugation of 6-[F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [F]F-Py-TFP, with rat albumin.

Bone marrow cell homing to sites of acute tibial fracture: Zr-oxine cell labeling with positron emission tomographic imaging in a mouse model.

Background: Bone fracture healing is dependent upon the rapid migration and engraftment of bone marrow (BM) progenitor and stem cells to the site of injury. Stromal cell-derived factor-1 plays a crucial role in recruiting BM cells expressing its receptor CXCR4. Recently, a CXCR4 antagonist, plerixafor, has been used to mobilize BM cells into the blood in efforts to enhance cell migration to sites of injury presumably improving healing.

The kinetics and reproducibility of 18F-sodium fluoride for oncology using current PET camera technology.

Unlabelled: We evaluated the kinetics of (18)F-sodium fluoride (NaF) and reassessed the recommended dose, optimal uptake period, and reproducibility using a current-generation PET/CT scanner.

Methods: In this prospective study, 73 patients (31 patients with multiple myeloma or myeloma precursor disease and 42 with prostate cancer) were injected with a mean administered dose of 141 MBq of (18)F-NaF. Sixty patients underwent 3 sequential sessions of 3-dimensional PET/CT of the torso beginning approximately 15 min after (18)F-NaF injection, followed by whole-body 3-dimensional PET/CT at 2 h.