Nuclear Medicine and Biology

INTRODUCTION: The widespread clinical utilization of 90 Y for preparation of target specific radiopharmaceuticals demands development of a facile, efficient and cost-effective method for radiochemical separation of 90 Y from 90 Sr via90 Sr/90 Y generator. In this article, we describe an efficient and facile method for radiochemical separation of 90 Y from 90 Sr for preparation of radiopharmaceuticals by exploiting the large difference in the solubility product constants (Ksp ) of Y(OH)3 and Sr(OH)2 ...

The relationship between cancer and inflammation is one of the most important fields for both clinical and translational research. Despite numerous studies reported interesting and solid data about the prognostic value of the presence of inflammatory infiltrate in cancers, the biological role of inflammation in prostate cancer development is not yet fully clarified. The characterization of molecular pathways that connect altered inflammatory response and prostate cancer progression can provide the scientific rationale for the identification of new prognostic and predictive biomarkers...

INTRODUCTION: meta-[123/131 I]Iodobenzylguanidine (mIBG) is a clinical agent used for imaging neuroendocrine tumors, where uptake in tumor is via active transport mechanism through norepinephrine transporters (NET). Our group in past have evaluated a 99m Tc-analogue of the above tracer, based on 99m Tc-4 + 1 labeling approach, which exhibited significant affinity for NET but suffered from reduced specific uptake in comparison to reference standard no-carrier-added (n.c.a.) [125 I]mIBG...

INTRODUCTION: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99m Tc-duramycin SPECT imaging. METHODS: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99m Tc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6)...

Recently, our research group reported on the development of 3β-[18 F]Fluorocholic acid (3β-[18 F]FCA), a 18 F labeled bile acid to detect drug interference with the bile acid transporters (drug-induced cholestasis). It was hypothesized that 3β-[18 F]FCA could also be used as a non-invasive tool to monitor (regional) liver function in vivo in different liver diseases through altered expression of bile acid transporters. METHODS: Hepatobiliary transport of 3β-[18 F]FCA was evaluated in four murine liver disease models...

INTRODUCTION: Multiple peptide receptors are co-expressed in many types of cancers. Arg-Gly-Asp (RGD) and GE11 peptides specifically target integrin αV β3 and EGFR, respectively. Recently, we designed and synthesized a heterodimer peptide NOTA-c(RGDyK)-GE11 (NOTA-RGD-GE11). The aim of this study was to investigate the characteristics of NOTA-RGD-GE11 for dual receptor imaging. METHODS: NOTA-RGD-GE11 heterodimer was labelled with 68 Ga. The dual receptor binding affinity was investigated by antibody competition binding assay...

INTRODUCTION: In this study, a new agent consisting of HER2-specific affibody ZHER2:V2 and chemotherapy drug pemetrexed was synthesized to develop a new targeted drug. Its biological characteristics and anticancer efficacy were assessed in cells level and xenografts models by radiolabeling with technetium-99m. METHODS: After the ZHER2:V2 -pemetrexed conjugate was synthesized, radiolabeling of the conjugate was performed using its C-terminal 4 amino acids (Gly-Gly-Gly-Cys) as the chelating moiety...

A pentapeptide macrocyclic ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for SPECT imaging and therapeutic in vivo agents. This study shows the synthesis and characterization of KYCAR complexes containing nonradioactive rhenium, 99m Tc, or 188 Re. The metal complexes were also biologically evaluated to determine in vivo distribution in healthy mice. The overall goals of this project were (1) to synthesize the Tc/Re pentapeptide complexes, (2) to identify spectroscopic methods for characterization of syn versus anti rhenium peptide complexes, (3) to analyze the ex vivo stability, and (4) to assess the biological properties of the [99m Tc]TcO-KYCAR and [188 Re]ReO-KYCAR complexes in vivo...

INTRODUCTION: Primary aldosteronism accounts for 6-15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst ~50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([11 C]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland...

INTRODUCTION: Poly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in prostate cancer (PC), such as mediating DNA damage repair, transcriptional regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help predict which patients are likely to respond to such therapy. Several PARP-1 positron emission tomography (PET) imaging agents have been developed and show promise for imaging PARP-1 expression in breast, brain, and lung cancer in small animals, but not as yet in prostate cancer...

INTRODUCTION: Our objective was to determine correlations between the tumor uptake and T/B ratios for 89 Zr-labeled T-DM1 (89 Zr-DFO-T-DM1) in mice with human BC xenografts by microPET/CT and biodistribution studies with HER2 expression and response to treatment with trastuzumab-DM1 (T-DM1). METHODS: The tumor and normal tissue uptake and T/B ratios for 89 Zr-DFO-T-DM1 (10 μg; 7.0 MBq) incorporated into a therapeutic dose (60 μg) were determined by microPET/CT and biodistribution studies at 96 h p...

INTRODUCTION: Adrenomedullin receptors are highly expressed in human alveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [18 F]AlF, for PET imaging of pulmonary microcirculation. METHODS: Highly concentrated [18 F](AlF)2+ (15 μL) was produced from purified fluorine-18 in NaCl 0.9%. Various complexation experiments were carried out at Al-to-NOTA molar ratios ranging from 1:1 to 1:40 to assess optimal radiolabeling conditions before using the peptide...

INTRODUCTION: Significant discrepancies between in vitro and in vivo binding of the muscarinic receptor ligand - 3 H-labeled Quinuclidinyl Benzilate (QNB) - have been well documented. Discernable in vivo cerebellar [3 H]QNB binding has been observed in mouse brain, despite the maximum number of binding sites (Bmax ) being low. In order to understand this unique in vivo binding phenomenon, the binding of two muscarinic receptor ligands - [3 H]QNB and N-[11 C]methylpiperidyl Benzilate ([11 C]NMPB) - were compared in vivo and in vitro in 3- and 8-week-old mice...

INTRODUCTION: 18 F-fluoroglycosylation via oxime formation is a chemoselective and mild radiolabeling method for sensitive molecules. Glycosylation can also improve the bioavailability, in vivo kinetics, and stability of the compound in blood, as well as accelerate clearance of biomolecules. A typical synthesis procedure for 18 F-fluoroglycosylation with [18 F]FDG (2-deoxy-2-[18 F]fluoro-d-glucose) and [18 F]FDR (5-deoxy-5-[18 F]fluoro-d-ribose) involves two HPLC (high performance liquid chromatography) purifications: one after 18 F-fluorination of the carbohydrate to remove its labeling precursor, and a second one after the oxime formation step to remove the aminooxy precursor...

INTRODUCTION: The natural amino acid l-Glutamine (Gln) is essential for both cell growth and proliferation. In addition to glucose, cancer cells utilize Gln as a carbon source for ATP production, biosynthesis, and as a defense against reactive oxygen species. The utilization of [11 C]Gln has been previously reported as a biomarker for tissues with an elevated demand for Gln, however, the previous reports for the preparation of [11 C]Gln were found to be lacking several crucial aspects necessary for transition to human production...

INTRODUCTION: Radiochemists/radiopharmacists, involved in the preparation of radiopharmaceuticals are regularly confronted with the requirement of continuous high quality productions in their day-to-day business. One of these requirements is high specific or molar activity of the radiotracer in order to avoid e.g. receptor saturation and pharmacological or even toxic effects of the applied tracer for positron emission tomography. In the case of 11 C-labeled radiotracers, the reasons for low molar activity are manifold and often the search for potential 12 C-contaminations is time-consuming...

INTRODUCTION: Neuroinflammation is associated with several neurological disorders, including Alzheimer's disease (AD). The translocator protein 18 kDa (TSPO), due to its overexpression during microglial activation and relatively low levels in the brain under normal neurophysiological conditions, is commonly used as an in vivo biomarker for neuroinflammation. Reported here is the preclinical evaluation of [18 F]F-DPA, a promising new TSPO-specific radioligand, as a tool for the detection of activated microglia at different ages in the APP/PS1-21 mouse model of AD and a blocking study to determine the specificity of the tracer...

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INTRODUCTION: The remarkable stability of the 89 Zr-DOTA complex has been shown in recent literature. The formation of this complex appears to require 89 Zr-chloride as the complexation precursor rather than the more conventional 89 Zr-oxalate. In this work we present a method for the direct isolation of 89 Zr-chloride from irradiated nat Y foils. METHODS: 89 Zr, 88 Zr, and 88 Y were prepared by 16 MeV proton irradiation of nat Y foils and used for batch-extraction based equilibrium coefficient measurements for TBP and UTEVA resin...

INTRODUCTION: The development of clinically useful tracers for PET imaging is enormously challenging and expensive. The intranasal (IN) route of administration is purported to be a viable route for delivering drugs to the brain but has, as yet, not been investigated for the delivery of PET tracers. If the intranasal (IN) pathway presents a viable option, it extends the PET imaging field by increasing the number of tracers available for human use. Here we report the results of a rodent study testing the feasibility of the IN route to administer radiotracers for brain PET imaging...