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Martin G Pomper

Publications and source records attributed to Martin G Pomper.

31 records · Page 2Linked to original sources
PubMed2003

Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria.

The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with I-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.

Animals↗
PubMed2003

Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging.

PURPOSE: To use combined proton (1H) and sodium 23 (23Na) magnetic resonance (MR) imaging to noninvasively quantify total tissue sodium concentration and to determine if concentration is altered in malignant human brain tumors. MATERIALS AND METHODS: Absolute tissue sodium concentration in malignant gliomas was measured on quantitative three-dimensional 23Na MR images with tissue identification from registered 1H MR images. Concentration was determined in gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and vitreous humor in 20 patients with pathologically proven malignant brain tumors (astrocytoma, n = 17; oligodendroglioma, n = 3) and in nine healthy volunteers. Sodium concentration in tumors and edema was determined from 23Na image signal intensities in regions that were contrast material enhanced on T1-weighted 1H images (tumors) or regions that were only hyperintense on fluid-attenuated inversion recovery (FLAIR) 1H images (edema). Sodium concentrations were measured noninvasively from 23Na images obtained with short echo times (0.4 msec) by using external saline solution phantoms for reference. Differences in mean sodium concentration of all healthy tissue and lesions in patients were tested with a paired t test. Concentration in uninvolved tissues in patients was compared with that in the same tissue types in the volunteers with an independent samples two-tailed t test. RESULTS: Mean concentration (in millimoles per kilogram wet weight) was 61 +/- 8 (SD) for GM, 69 +/- 10 for WM, 135 +/- 10 for CSF, 113 +/- 14 for vitreous humor, 103 +/- 36 for tumor, 68 +/- 11 for unaffected contralateral tissue, and 98 +/- 12 for FLAIR hyperintense regions surrounding tumors. Significant differences (P <.002) in sodium concentration were demonstrated by using a t test for both tumors and surrounding FLAIR hyperintense tissues versus GM, WM, CSF, and contralateral brain tissue. CONCLUSION: 23Na MR imaging with short echo times can be used to quantify absolute tissue sodium concentration in patients with brain tumors and shows increased sodium concentration in tumors relative to that in normal brain structures.

Adolescent↗
PubMed2003

The surgical bed after BCNU polymer wafer placement for recurrent glioma: serial assessment on CT and MR imaging.

OBJECTIVE: The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS: The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS: Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION: BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.

Adult↗
PubMed2002

Brain white matter anatomy of tumor patients evaluated with diffusion tensor imaging.

We applied multislice, whole-brain diffusion tensor imaging (DTI) to two patients with anaplastic astrocytoma. Data were analyzed using DTI-based, color-coded images and a 3-D tract reconstruction technique for the study of altered white matter anatomy. Each tumor was near two major white matter tracts, namely, the superior longitudinal fasciculus and the corona radiata. Those tracts were identified using the color-coded maps, and spatial relationships with the tumors were characterized. In one patient the tumor displaced adjacent white matter tracts, whereas in the other it infiltrated the superior longitudinal fasciclus without displacement of white matter. DTI provides new information regarding the detailed relationship between tumor growth and nearby white matter tracts, which may be useful for preoperative planning.

Adult↗
PubMed2002

Can small animal imaging accelerate drug development?

Better mechanistic understanding of disease through mapping of the human and mouse genomes enables rethinking of human infirmity. In the case of cancer, for example, we may begin to associate disease states with their underlying genetic defects rather than with the organ system involved. That will enable more selective, nontoxic therapies in patients who are genetically predisposed to respond to them. Because one of the major goals of molecular imaging research is to interrogate gene expression noninvasively, it can impact greatly on that process. Most of molecular imaging research is undertaken in small animals, which provide a conduit between in vitro studies and human clinical imaging. We are fortunate to be able to manipulate small animals genetically, and to have increasingly better models of human disease. The ability to study those animals noninvasively and quantitatively with new, high-resolution imaging devices provides the most relevant milieu in which to find and examine new therapies.

Animals↗
PubMed2002

Quantitative MR spectroscopic imaging of brain lesions in patients with AIDS: correlation with [11C-methyl]thymidine PET and thallium-201 SPECT.

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the metabolic basis for magnetic resonance (MR) spectroscopic imaging findings in focal brain lesions of patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The authors combined MR spectroscopic imaging with [11C-methyl]thymidine positron emission tomography (PET) and thallium-201 single photon emission computed tomography (SPECT) in 10 patients. They sought a characteristic metabolite profile that would enable differentiation of benign lesions from primary central nervous system lymphoma and determined whether PET and SPECT results supported the MR spectroscopic imaging findings. RESULTS: Metabolite compositions of the lesions were similar, likely because the lesions were late stage and tended to be necrotic. Brain lesions in patients with AIDS were nonspecific regarding metabolic profile as determined with MR spectroscopic imaging. All patients with positive PET and SPECT studies had primary central nervous system lymphoma. CONCLUSION: PET and SPECT may be more reliable than MR spectroscopic imaging for differentiating benign lesions from primary central nervous system lymphoma in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma.

SUMMARY: Astroblastoma is a rare primary glial tumor with a characteristic appearance on neuroradiologic images. Typically, astroblastomas are large, lobulated, peripheral, supratentorial, solid, and cystic masses with relatively little associated vasogenic edema and tumor infiltration for their large size. The solid component of the mass has a bubbly appearance and a T2 signal that is isointense to gray matter. Punctate calcifications are often present. Neuroradiologists should be familiar with the characteristic appearance of this tumor.

Adolescent↗
PubMedDate not supplied

Predicting the success of a radiopharmaceutical for in vivo imaging of central nervous system neuroreceptor systems.

In vivo imaging of the central nervous system (CNS) neuroreceptors in humans began was used in the early 1980s. Now, some twenty years later, the success of radiopharmaceutical imaging is still often one based on empiricism and serendipity. Nevertheless, a number of factors can be identified based on the robot experience in developing these radiotracers. This article will describe some of the issues that may be useful in choosing approaches to radiolabel ligands as future imaging agents of neuroreceptors, transporters and intrasynaptic measures of neurotransmitters. A description of the current process from hypothesis to radiochemical preclinical development, non-human primate imaging development of quantitative procedures finally leading to toxicology, dosimetry and eventually human applications are provided. The role of important factors including metabolism and lipophilicity, affinity and other factors for optimizing radiolabeling strategies is dealt with. Furthermore, issues involving decision making of how far to extend efforts in developing a radiotracer and when might be an appropriate stopping place are discussed. Finally some typical examples of the use of these radiotracers, especially with emphasis on stable drug design and development, are provided. These include occupancy studies and mechanism of action studies. In summary, the prediction of tracer success includes: first, identification of appropriate targets and precursors, then systematic optimization of ligands with continuous feedback from pharmacokinetics and iterative improvement based on unsuccessful tracers. This article is intended to present a pragmatic overview of the radiopharmaceutical development process with emphasis on the CNS.

Animals↗
PubMedDate not supplied

11C-MCG: synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase).

Imaging of glutamate carboxypeptidase II (GCP II), also known as N-acetylated alpha-linked L-amino dipeptidase (NAALADase), may enable study of glutamatergic transmission, prostate cancer, and tumor neovasculature in vivo. Our goal was to develop a probe for GCP II for use with positron emission tomography (PET). Radiosynthesis of 11C-MeCys-C(O)-Glu or 11C-(S)-2-[3-((R)-1-carboxy-2-methylsulfanyl-ethyl)-ureido]-pentanedioic acid (11C-MCG), an asymmetric urea and potent (Ki = 1.9 nM) inhibitor of GCP II, was performed by C-11 methylation of the free thiol. Biodistribution of 11C-MCG was assayed in mice, and quantitative PET was performed in a baboon. 11C-MCG was obtained in 16% radiochemical yield at the end of synthesis with specific radioactivities over 167 GBq/mmol (4000 Ci/mmol) within 30 min after the end of bombardment. At 30 min postinjection, 11C-MCG showed 33.0 +/- 5.1%, 0.4 +/- 0.1%, and 1.1 +/- 0.2% ID/g in mouse kidney (target tissue), muscle, and blood, respectively. Little radioactivity gained access to the brain. Blockade with unlabeled MCG or 2-(phosphonomethyl)pentanedioic acid (PMPA), another potent inhibitor of GCP II, provided sevenfold and threefold reductions, respectively, in binding to target tissue. For PET, distribution volumes (DVs) were 1.38 then 0.87 pre- and postblocker (PMPA). Little metabolism of 11C-MCG occurred in the mouse or baboon. These results suggest that 11C-MCG may be useful for imaging GCP II in the periphery.

Analysis of Variance↗
PubMedDate not supplied

In vivo imaging of peripheral benzodiazepine receptors in mouse lungs: a biomarker of inflammation.

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [(123)I]-(R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals (p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [(11)C]-(R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

Animals↗