Radioiodination via isotope exchange in pivalic acid

A variety of benzoic and aryl aliphatic mono and polyiodinated acids and esters (sterol, triglyceride) were radioiodinated in 55-99% radiochemical yield by isotope exchange with Na 125I in a melt of pivalic acid. In general, the reaction was complete in 1 h at 155[deg]C with little or no substrate decompostion. High specific activity studies afforded 125I-labeled iopanoic acid with a specific activity of over 700 Ci/mmol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26445/1/0000533.pd

Formulation of Polyiodinated Triglyceride Analogues in a Chylomicron Remnant-Like Liver-Selective Delivery Vehicle

Purpose . A formulation methodology for the incorporation of polyiodinated triglyceride (ITG) analogues into a protein-free chylomicron remnant-like emulsion was developed to provide a vehicle for the selective hepatic delivery of these agents for contrast-enhanced X-ray computed tomography (CECT).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41452/1/11095_2004_Article_306640.pd

Radioiodinated Cholesteryl lopanoate as a Potential Probe for the in Vivo Visualization of Atherosclerotic Lesions in Animals

Radioiodinated cholesteryl iopanoate, a nonhydrolyzable cholesteryl ester probe, showed increased uptake into atherosclerotic aortas of cholesterol-fed rabbits in comparison with normal rabbits. Auto-radiography of the aortas showed the radioactivity to be concentrated in areas of visible atherosclerotic involvement. Lipid extraction and thin-layer chromatography of this tissue as well as liver, adrenal, and plasma confirmed the resistance of this probe to hydrolysis. These findings suggest that 125 I-cholesteryl iopanoate may prove useful for noninvasively monitoring atherosclerosis in intact laboratory animals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41511/1/11095_2004_Article_306434.pd

Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment

Targeted radionuclide therapy (TRT) and immunotherapy are rapidly growing classes of cancer treatments. Basic, translational, and clinical research are now investigating therapeutic combinations of these agents. In comparison to external beam radiation therapy (EBRT), TRT has the unique advantage of treating all disease sites following intravenous injection and selective tumor uptake and retention—a particularly beneficial property in metastatic disease settings. The therapeutic value of combining radiation therapy with immune checkpoint blockade to treat metastases has been demonstrated in preclinical studies, whereas results of clinical studies have been mixed. Several clinical trials combining TRT and immune checkpoint blockade have been initiated based on preclinical studies combining these with EBRT and/or TRT. Despite the interest in translation of TRT and immunotherapy combinations, many questions remain surrounding the mechanisms of interaction and the optimal approach to clinical implementation of these combinations. This review highlights the mechanisms of interaction between anti-tumor immunity and radiation therapy and the status of basic and translational research and clinical trials investigating combinations of TRT and immunotherapies

Effect of Polar Head Group Modifications on the Tumor Retention of Phospholipid Ether Analogs: Role of the Quaternary Nitrogen

We have previously described the remarkable capacity of radioiodinated alkyl phospholipids to be sequestered and retained by a variety of tumors in vivo. We have already established the influence of certain structural parameters of iodinated alkyl phospholipids on tumor avidity, such as stereochemistry at the sn-2 carbon of alkylglycerol phosphocholines, meta-or para-position of iodine in the aromatic ring of phenylalkyl phosphocholines, and the length of the alkyl chain in alkyl phospholipids. In order to determine the additional structural requirements for tumor uptake and retention, three new radioiodinated alkylphospholipid analogs, 2–4, were synthesized as potential tumor imaging agents. Polar head groups were modified to determine structure-tumor avidity relationships. The trimethylammonio group in 1 was substituted with a hydrogen atom in 2, an ammonio group in 3 and a tertiary butyl group in 4. All analogs were separately labeled with iodine-125 or iodine-124 and administered to Walker 256 tumor-bearing rats or human PC-3 tumor-bearing SCID mice, respectively. Tumor uptake was assessed by gamma-camera scintigraphy (for [I-125]-labeled compounds) and high-resolution micro-PET scanning (for [I-124]-labeled compounds). It was found that structural modifications in the polar head group of alkyl phospholipids strongly influenced the tumor uptake and tissue distribution of these compounds in tumor-bearing animals. Phosphoethanolamine analog 3 (NM401) displayed a very slight accumulation in tumor as compared with phosphocholine analog 1 (NM346). Analogs 2 (NM400) and 4 (NM402) lacking the positively charged nitrogen atom failed to display any tumor uptake and localized primarily in the liver. This study provided important insights regarding structural requirements for tumor uptake and retention. Replacement of the quaternary nitrogen in the alkyl phospholipid head group with non-polar substituents resulted in loss of tumor avidity