Copper-62 labeled ReCCMSH peptide analogs for melanoma PET imaging.

High-specific activity radiolabeled melanocortin peptide preparations are necessary for optimal melanoma imaging due to the relatively low number of melanocortin-1 receptors (MC1-Rs) per tumor cell. In this study, a one-step synthesis of 62Cu-labeled MC1-R targeting peptide Re(Arg11)CCMSH was developed, which yielded high specific activity radiolabeled peptide preparations that required no post-labeling purification. DOTA and NOTA conjugated Re(Arg11)CCMSH peptides were synthesized and examined for 62Cu radiolabeling and cell binding properties.

Non-invasive microCT imaging characterization and in vivo targeting of BB2 receptor expression of a PC-3 bone metastasis model.

Purpose: A devastating progression of human prostate cancer is the development of bone metastasis. Animal models of bone metastasis induced by inoculating human prostate cell lines into mice are well established. Here, we report the characterization of a mouse model of prostatic bone metastasis using non-invasive microCT and targeted microSPECT imaging of bone tumors using the bombesin receptor (BB2r)-avid radiolabeled peptide, (111)In-DOTA-8-Aoc-BBN[7–14]NH(2).

Evaluation of 99mTc-glucarate as a breast cancer imaging agent in a xenograft animal model.

Introduction: The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [(99m)Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [(99m)Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors.

Comparative evaluation of three 64Cu-labeled E. coli heat-stable enterotoxin analogues for PET imaging of colorectal cancer.

Analogues of the E. coli heat-stable enterotoxin (STh) are currently under study as both imaging and therapeutic agents for colorectal cancer. Studies have shown that the guanylate cyclase C (GC-C) receptor is commonly expressed in colorectal cancers.

In vivo imaging of human colorectal cancer using radiolabeled analogs of the uroguanylin peptide hormone.

Background: Uroguanylin is an endogenous peptide agonist that binds to the guanylate cyclase C receptor (GC-C). GC-C is overexpressed in human colorectal cancer (CRC), and exposure of GC-C-expressing cells to GC-C agonists results in cell cycle arrest and/or apoptosis, highlighting the therapeutic potential of such compounds. This study describes the first use of radiolabeled uroguanylin analogs for in vivo detection of CRC.

TLD assessment of mouse dosimetry during microCT imaging.

Advances in laboratory animal imaging have provided new resources for noninvasive biomedical research. Among these technologies is microcomputed tomography (microCT) which is widely used to obtain high resolution anatomic images of small animals. Because microCT utilizes ionizing radiation for image formation, radiation exposure during imaging is a concern.

Design, synthesis, and biological evaluation of an antagonist-bombesin analogue as targeting vector.

The gastrin releasing peptide receptor (GRP-R) is overexpressed on a number of tumors and cancer cell lines including pancreas, prostate, breast, gastrointestinal, and small cell lung cancer (SCLC). Radiolabeled bombesin (BBN) analogues have exhibited high binding affinity and specificity to the GRP-R. A bombesin analogue with an antagonist targeting vector at the C-terminus, DOTA-aminohexanoyl-[D-Phe(6), Leu-NHCH 2CH 2CH3(13), des Met(14)] BBN[6-14] (1, "Bomproamide"), has been synthesized and displays high binding affinity (IC50 = 1.

Evaluation of the pharmacokinetic effects of various linking group using the 111In-DOTA-X-BBN(7-14)NH2 structural paradigm in a prostate cancer model.

The high incidence of BB2 receptor (BB2r) expression in various cancers has prompted investigators to pursue the development of BB2r-targeted agents for diagnostic imaging, chemotherapy, and radiotherapy. Development of BB2r-targeted agents, based on the bombesin (BBN) peptide, has largely involved the use of the bifunctional chelate approach in which the linking group serves several key roles including pharmacokinetic modification. Understanding the in vivo properties of the various pharmacokinetic modifying linking groups is crucial for developing BB2r-targeted agents with improved targeting and clearance characteristics.

Molecular imaging of bcl-2 expression in small lymphocytic lymphoma using 111In-labeled PNA-peptide conjugates.

Unlabelled: The bcl-2 gene is overexpressed in non-Hodgkin's lymphoma (NHL), such as small lymphocytic lymphoma (SLL), and many other cancers. Noninvasive imaging of bcl-2 expression has the potential to identify patients at risk for relapse or treatment failure. The purpose of this study was to synthesize and evaluate radiolabeled peptide nucleic acid (PNA)-peptide conjugates targeting bcl-2 gene expression.

Metabolic derangements in the insulin-resistant heart.

Myocardium is flexible when it comes to energy substrate utilization; it uses fatty acid, glucose, lactones, and ketones for its energy requirement. The myocardial energy substrate preference varies in a dynamic manner depending on myocardial perfusion, energy demand, substrate availability, and local/systemic hormonal changes. The authors discuss the metabolic perturbations seen in insulin-resistant myocardium and how they result in structural and other biochemical changes that ultimately result in left ventricular hypertrophy and diastolic and systolic dysfunction.

In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems.

Unlabelled: The BB2 receptor subtype, of the bombesin family of receptors, has been shown to be highly overexpressed in a variety of human tumors, including prostate cancer. Bombesin (BBN), a 14-amino acid peptide, has been shown to target the BB2 receptor with high affinity. 64Cu (half-life = 12.

Selective targeting of E. coli heat-stable enterotoxin analogs to human colon cancer cells.

Background: Radiolabeled analogs of the E. coli heat-stable enterotoxin (ST(h)) are currently under study as imaging and therapeutic agents for colorectal cancer. The aim of these studies is to compare in vitro and in vivo characteristics of two novel ST(h) analogs with appended DOTA chelating moieties.

Microimaging characterization of a B16-F10 melanoma metastasis mouse model.

Metastatic mouse models of melanoma have been characterized by gross necropsy examination, histopathology, and optical imaging. To determine if the time progression, extent, and metabolism of melanoma metastases could be monitored noninvasively, serial micro-CT and small-animal PET imaging studies were performed by using a mouse model of melanoma. Juvenile female C57BL/6 mice were injected intravenously with syngenic B16-F10 melanoma cells.

Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety.

We have described the synthesis of tridentate pyrazolyl ligand frameworks for coordination to the fac-[*M(CO)(3)](+) metal fragment (*M=(186/188)Re or (99m)Tc). These ligands impart a degree of kinetic inertness on the metal center, warranting their study in biological systems. We herein report in vitro/in vivo radiolabeling investigations of a new series of pyrazolyl bombesin (BBN) conjugates radiolabeled via the Isolink kit.