Biomedical subjects

I Al-Jammaz

Publications and source records attributed to I Al-Jammaz.

8 recordsLinked to original sources

PubMed2006

Synthesis and evaluation of radioiodinated substituted beta-naphthylalanine as a potential probe for pancreatic beta-cells imaging.

A non-invasive imaging technique capable of relating a signal from the beta-cells to their mass will be of immense value in understanding the progression of diabetes. Several molecular markers have indeed been identified and investigations are ongoing aimed at accomplishing the said goal. These include pancreatic islet antigen (IC-2), somatostatin receptors (SSTRs), and sulfonylurea receptors (SURs) on the pancreatic beta-cells. Therefore investigations exploiting the potential application of the radiolabeled ligands for these receptors for beta-cell imaging are receiving intensive research attention. Radioiodinated peptidomimetic based on beta-naphthylalanine and n-hexanediamine has been synthesized. The molecule was subjected to in vitro and in vivo evaluation. Radioligand binding studies on CHO cell line expressing the SSTR2 showed very low affinity. Nonetheless, biodistribution in normal mice showed significant uptake in the pancreas. There was partial blockage of the pancreatic uptake when excess of the peptidomimetic was coinjected. The result implies that the pancreatic uptake was receptor mediated but may not involve the SSTR2 and therefore warrants further investigation.

Animals↗

PubMed2005

Synthesis and biodistribution of 2-[123I]iodomelatonin in normal mice.

Melatonin demands that this hormone and its receptors be well understood. With this aim in mind, synthetic melatonin was radioiodinated with no-carrier-added (n.c.a.) sodium iodide-123 using in situ generated peracetic acid as oxidizing agent for electrophilic iodination at room temperature. The radiochemical yield was typically greater than 80% after 20 min reaction time especially when relatively small amounts of activities were used (<or=10 mCi). Biological evaluation was performed in normal mice. The distribution of the tracer did not reveal any specificity during the time frame studied. There was no significant retention in the whole brain.

Animals↗

PubMed2005

Prosthetic radioiodination of interleukin-8 ([(123/131)I]-IL-8): biological behavior in a mouse infection model.

Numerous molecular entities with diverse structures have been radiolabeled and investigated as potential infection and inflammation detection agents. However, none of these molecules have gained the acceptance of gallium citrate or radiolabeled autologous white blood cells. We have radioiodinated interleukin-8 using two different methods and tested the biological behavior of the products in mice. As expected, the direct radioiodinated material displayed extensive in vivo deiodination. The use of pyridine-based prosthetic label yielded a product with better kinetics than the direct radioiodination method and showed a better target to non-target ratio. Nonetheless, this method is not suited for labeling of bioactive peptides such as the title peptide because of the very high specific activity required to prevent cytotoxic effects in a human application.

Animals↗

PubMed2004

2-[(18)F]-fluoroisonicotinic acid hydrazide: biological evaluation in an acute infection model.

We have synthesized 2-[(18)F]-fluoroisonicotinic acid hydrazide by nucleophilic displacement reaction on ethyl-2- (trimethylammonium)-isonicotinate precursor in acetonitrile. Kryptofix 222 was used as the phase transfer catalyst. The intermediate fluorinated ethyl ester reacted with hydrazine hydrate to produce the hydrazide. Excellent radiochemical yield was attained with total synthesis time of approximately 60 min. Biological evaluation was performed in bacterial cells and biodistribution in normal as well as E. coli infected CBA/J mice. It was found that the S. pneumoniae cells retained the radiotracer in an in vitro assay. The tracer showed positive localization at the infection/inflammation site in E. coli infected mice.

Animals↗

PubMed2002

A novel route to radioiodinated [123I]-N-succinimidyl-3-iodobenzoate, a reagent for radioiodination of bioactive peptides.

Radiolabeled peptides continue to emerge as potential radiopharmaceuticals for targeting several diseases such as cancer, infection and inflammation and even tissue and organ rejection. The classical method for labeling these molecules has been the electrophilic route. Evidence suggests that most molecules labeled via this route perturb their biological activity. Moreover, this method is not applicable to peptides lacking a tyrosine moiety in their structure. Hence, there is the need to develop alternate methods such as the prosthetic approach. We have optimized a solid-state radioiodination by exchange to produce [123I]-metaiodobenzylguanidine ([123I]-mIBG). The mIBG served as a precursor to obtain an activated N-succinimidyl ester for efficient coupling to amine functions in peptides, preferably the lysine group(s). The method was used to label a model chemotactic peptide and evaluated in vivo.

Animals↗

PubMed2002

Novel synthesis of 2-[18F]-fluoroisonicotinic acid hydrazide and initial biological evaluation.

2-[18F]-Fluoroisonicotinic acid hydrazide was synthesized by nucleophilic displacement reaction on ethyl-2- (trimethylammonium)-isonicotinate precursor in acetonitrile. Kryptofix 222 was used as the phase transfer catalyst. The intermediate fluorinated ethyl ester reacted with hydrazine hydrate to produce the hydrazide in excellent radiochemical yield. The overall radiochemical yield was greater than 70% with total synthesis time of approximately 60 minutes. Biological evaluation was performed in bacterial cells and biodistribution in normal CBA/J mice. It was found that the S. pneumoniae cells retained the radiotracer in an in vitro assay.

Animals↗

PubMed2001

An efficient batch preparation of high specific activity.

The increasing demand for radiolabeled metaiodobenzylguanidine (mIBG) prompted the need to obtain the radiopharmaceutical by a reliable, routine and simple synthetic method for batch production. The production of mIBG labeled with either 123I or 124I has been optimized by modifying literature methods that involve solid-state exchange reaction on "cold" mIBG facilitated by ammonium sulfate. The radiochemical yield and purity of radioiodinated mIBG generally exceeded 80 and 98%, respectively, with specific activity of > 50 mCi/mg.

3-Iodobenzylguanidine↗

PubMed2001

Synthesis and preliminary evaluation of Tc-99m-labeled somatostatin analog (RC-160) using "3+1" mixed ligand approach.

The success of (111)In-pentetreotide as a cancer-imaging agent has given impetus to the search for other peptide-based radiopharmaceuticals. The labeling with Tc-99m has become even more attractive because of the ready availability and near ideal physical properties. Additionally, the kinetics of the peptide-receptor interactions favors the radiolabeling with technetium-99m. A somatostatin analog RC-160 has been labeled with Tc-99m using the "3+1" mixed ligand approach utilizing the NNS/S coordination sites. The ternary complex was formed in greater than 95% within 30 min by simultaneous reduction and complexation of technetium-99m pertechnetate. The Tc-99m and the surrogate rhenium complexes showed similar chromatographic behavior. The complex was evaluated by in vitro receptor binding studies carried out on HTB-121 breast cancer cell line and biodistribution studies performed in normal mice. Our findings suggest that RC-160 can be labeled by the mixed ligand approach with the complex retaining its biological activity and warrants further studies.

Animals↗