John L Humm

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (208)895.93 Total impact

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    ABSTRACT: Methods: Six patients with squamous cell carcinoma of the head and neck and ten HT29 colorectal carcinoma-bearing nude rats were studied. In addition to an (18)F-fluorodeoxyglucose PET scan, each patient underwent a 45-min (18)F-fluoromisonidazole dPET scan, followed by 10 min acquisitions at 96±4 and 163±17 min post-injection. Ninety-minute (18)F-fluoromisonidazole dPET acquisitions were performed in animals. Intra-tumor voxels were classified into 4 clusters based on their kinetic behavior using k-means clustering. Kinetic modeling was carried out using the foregoing full datasets (FD) and repeated for each of two shortened datasets corresponding to the first ~100 min (SD1; patients only) or the first 45 min (SD2) of dPET data. The kinetic rate constants (KRCs) as calculated with a 2-compartment model for both SD1 and SD2 were compared to those derived from FD by correlation (Pearson), regression (Passing-Bablok), deviation (Bland-Altman) and classification (area under receiver operating characteristic curve; AUC) analyses. Simulations were performed to assess uncertainties due to statistical noise. Results: Strong correlation (r≥0.75, p<0.001) existed between all KRCs deduced from both SD1 and SD2, and from FD. Significant differences between KRCs were only found for FD-SD2 correlations in patient studies. K1 and k3 were reproducible to within ~6% and ~30% (FD-SD1; patients) and ~4% and ~75% (FD-SD2; animals). AUC values for classification of patient clusters as hypoxic, using a tumor-to-blood ratio>1.2, were 0.91 (SD1) and 0.86 (SD2). The percentage standard deviation in estimating K1 and k3 from 45-min shortened datasets due to noise was <1% and between 2-12% respectively. Conclusion: Using single-session 45-min shortened (18)F-fluoromisonidazole dynamic PET datasets appears to be adequate for the identification of intra-tumor regions of hypoxia. However, k3 was significantly overestimated in the clinical cohort. Further studies are necessary to evaluate the clinical significance of differences between the results as calculated from full and shortened datasets.
    No preview · Article · Nov 2015 · Journal of Nuclear Medicine
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    ABSTRACT: This work describes PETSTEP (PET Simulator of Tracers via Emission Projection): a faster and more accessible alternative to Monte Carlo (MC) simulation generating realistic PET images, for studies assessing image features and segmentation techniques. PETSTEP was implemented within Matlab as open source software. It allows generating three-dimensional PET images from PET/CT data or synthetic CT and PET maps, with user-drawn lesions and user-set acquisition and reconstruction parameters. PETSTEP was used to reproduce images of the NEMA body phantom acquired on a GE Discovery 690 PET/CT scanner, and simulated with MC for the GE Discovery LS scanner, and to generate realistic Head and Neck scans. Finally the sensitivity (S) and Positive Predictive Value (PPV) of three automatic segmentation methods were compared when applied to the scanner-acquired and PETSTEP-simulated NEMA images. PETSTEP produced 3D phantom and clinical images within 4 and 6 min respectively on a single core 2.7 GHz computer. PETSTEP images of the NEMA phantom had mean intensities within 2% of the scanner-acquired image for both background and largest insert, and 16% larger background Full Width at Half Maximum. Similar results were obtained when comparing PETSTEP images to MC simulated data. The S and PPV obtained with simulated phantom images were statistically significantly lower than for the original images, but led to the same conclusions with respect to the evaluated segmentation methods. PETSTEP allows fast simulation of synthetic images reproducing scanner-acquired PET data and shows great promise for the evaluation of PET segmentation methods. Copyright © 2015 Associazione Italiana di Fisica Medica. All rights reserved.
    Full-text · Article · Aug 2015 · Physica Medica
  • Robin M Kramer · James Russell · John L Humm
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    ABSTRACT: Pancreatic cancer is one of the leading causes of cancer-related death in the United States. Gemcitabine is a common treatment, but response rates are low, perhaps due in part to tumor hypoxia. We utilized (14)C-labeled gemcitabine to map distribution of the drug with respect to perfused and hypoxic regions of the tumor microenvironment in two orthotopic xenograft models of pancreatic cancer. There was only a slight reduction in gemcitabine in hypoxic areas, with ∼78% of the drug present in hypoxic compared to perfused areas. In addition, only a 4% reduction in gemcitabine was measured at >100 μm from perfused blood vessels. Thus, despite significant areas of hypoxia in these tumors, gemcitabine distribution is relatively homogenous. Ours is the first study to directly measure gemcitabine distribution within tumor tissue, demonstrating that in these models, tumor tissue does not represent a barrier to gemcitabine penetration.
    No preview · Article · Jul 2015 · Cancer Biotherapy & Radiopharmaceuticals
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    ABSTRACT: The molecular specificity of monoclonal antibodies (mAbs) directed against tumor antigens has proven effective for targeted therapy of human cancers, as shown by a growing list of successful antibody-based drug products. We describe a novel, nonlinear compartmental model using PET-derived data to determine the "best-fit" parameters and model-derived quantities for optimizing biodistribution of intravenously injected (124)I-labeled antitumor antibodies. As an example of this paradigm, quantitative image and kinetic analyses of anti-A33 humanized mAb (also known as "A33") were performed in 11 colorectal cancer patients. Serial whole-body PET scans of (124)I-labeled A33 and blood samples were acquired and the resulting tissue time-activity data for each patient were fit to a nonlinear compartmental model using the SAAM II computer code. Excellent agreement was observed between fitted and measured parameters of tumor uptake, "off-target" uptake in bowel mucosa, blood clearance, tumor antigen levels, and percent antigen occupancy. This approach should be generally applicable to antibody-antigen systems in human tumors for which the masses of antigen-expressing tumor and of normal tissues can be estimated and for which antibody kinetics can be measured with PET. Ultimately, based on each patient's resulting "best-fit" nonlinear model, a patient-specific optimum mAb dose (in micromoles, for example) may be derived.
    No preview · Article · Jul 2015 · European Journal of Nuclear Medicine
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    ABSTRACT: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Although spatially precise systems are now available for small-animal irradiations, there are currently limited software tools available for treatment planning for such irradiations. We report on the adaptation, commissioning, and evaluation of a 3-dimensional treatment planning system for use with a small-animal irradiation system. The 225-kV X-ray beam of the X-RAD 225Cx microirradiator (Precision X-Ray) was commissioned using both ion-chamber and radiochromic film for 10 different collimators ranging in field size from 1 mm in diameter to 40 × 40 mm(2). A clinical 3-dimensional treatment planning system (Metropolis) developed at our institution was adapted to small-animal irradiation by making it compatible with the dimensions of mice and rats, modeling the microirradiator beam orientations and collimators, and incorporating the measured beam data for dose calculation. Dose calculations in Metropolis were verified by comparison with measurements in phantoms. Treatment plans for irradiation of a tumor-bearing mouse were generated with both the Metropolis and the vendor-supplied software. The calculated beam-on times and the plan evaluation tools were compared. The dose rate at the central axis ranges from 74 to 365 cGy/min depending on the collimator size. Doses calculated with Metropolis agreed with phantom measurements within 3% for all collimators. The beam-on times calculated by Metropolis and the vendor-supplied software agreed within 1% at the isocenter. The modified 3-dimensional treatment planning system provides better visualization of the relationship between the X-ray beams and the small-animal anatomy as well as more complete dosimetric information on target tissues and organs at risk. It thereby enhances the potential of image-guided microirradiator systems for evaluation of dose-response relationships and for preclinical experimentation generally. © The Author(s) 2015.
    No preview · Article · May 2015 · Technology in cancer research & treatment
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    ABSTRACT: Radionecrosis is a potentially devastating complication of external beam radiotherapy (XRT). Intraventricular compartmental radioimmunotherapy (cRIT) using (131)I-3F8 or (131)I-8H9 can eradicate malignant cells in the CSF. The incidence of radionecrosis using cRIT (131)I based intraventricular radioimmunotherapy, when used alone or in combination with conventional craniospinal CSI-XRT is unknown. We retrospectively analyzed the incidence of radionecrosis in two cohorts of pediatric patients treated with both CSI-XRT and cRIT at MSKCC since 2003: patients with metastatic CNS neuroblastoma (NB) and medulloblastoma (MB). 94 patients received both CSI-XRT and cRIT, two received cRIT alone, median follow up 41.5 months (6.5-124.8 months). Mean CSI-XRT dose was 28 Gy (boost to the primary tumor site up to 54 Gy) in the MB cohort, and CSI XRT dose 18-21 Gy (boost to 30 Gy for focal parenchymal mass) in the NB cohort. For MB patients, 20 % had focal re-irradiation for a second or more subsequent relapse, mean repeat-XRT dose was 27.5 Gy; seven patients with NB had additional focal XRT. Median CSF cRIT dose was 18.6 Gy in the MB cohort and 32.1 in the NB cohort. One asymptomatic patient underwent resection of 0.6-cm hemorrhagic periventricular white-matter lesion confirmed to be necrosis and granulation tissue, 2.5 years after XRT. The risk of radionecrosis in children treated with XRT and cRIT appears minimal (~1 %). No neurologic deficits secondary to radionecrosis have been observed in long-term survivors treated with both modalities, including patients who underwent re-XRT. Administration of cRIT may safely proceed in patients treated with conventional radiotherapy without appearing to increase the risk of radionecrosis.
    No preview · Article · May 2015 · Journal of Neuro-Oncology

  • No preview · Conference Paper · May 2015
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    ABSTRACT: The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for (226)Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · International journal of radiation oncology, biology, physics
  • Sean Carlin · John Humm

    No preview · Article · Mar 2015
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    ABSTRACT: Core biopsies obtained using PET/CT guidance contain bound radiotracer and therefore provide information about tracer uptake in situ. Our goal is to develop a method for Quantitative Autoradiography of Biopsy Specimens (QABS), to use this method to correlate (18)F-fluorodeoxyglucose (FDG) tracer uptake in situ with histopathology findings, and to briefly discuss its potential application. Twenty seven (27) patients referred for a PET/CT-guided biopsy of FDG-avid primary or metastatic lesions in different locations consented to participate in this institutional review board-approved, HIPAA compliant study. Autoradiography (ARG) of biopsy specimens obtained using five types of needles was performed immediately after extraction. The response of ARG imaging plates was calibrated using dummy specimens with known activity obtained using two core biopsy needle sizes. The calibration curves were used to quantify the activity along biopsy specimens obtained with these two needles and to calculate standardized uptake values, SUVARG. ARG images were correlated with histopathologic findings and fused with PET/CT images demonstrating the position of the biopsy needle within the lesion. Logistic regression analysis was performed to search for SUVARG threshold distinguishing benign from malignant tissue in liver biopsy specimens. Pearson correlation between SUVARG of the whole biopsy specimen and average SUVPET over the voxels intersected by the needle in the fused PET/CT was calculated. Activity concentrations were obtained using ARG for 20 specimens extracted with 18G and 20G needles. The probability for finding malignancy in a specimen is larger than 50% (95 % confidence) if SUVARG is larger than 7.3. For core specimens with preserved shape and orientation and in the absence of motion, ARG, CT and PET images registration with spatial accuracy better than 2 mm is achievable. The correlation coefficient between specimen mean SUVARG and SUVPET was 0.66. Performing QABS on core biopsy specimens obtained using PET/CT guidance enables in situ correlation of FDG tracer uptake and histopathology on a millimeter scale. QABS promises to provide useful information for guiding interventional radiology procedures and localized therapies and for in situ high spatial resolution validation of radiopharmaceuticals uptake. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Full-text · Article · Feb 2015 · Journal of Nuclear Medicine
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    ABSTRACT: A first-in-human clinical trial of ultrasmall inorganic hybrid nanoparticles, "C dots" (Cornell dots), in patients with metastatic melanoma is described for the imaging of cancer. These renally excreted silica particles were labeled with (124)I for positron emission tomography (PET) imaging and modified with cRGDY peptides for molecular targeting. (124)I-cRGDY-PEG-C dot particles are inherently fluorescent, containing the dye, Cy5, so they may be used as hybrid PET-optical imaging agents for lesion detection, cancer staging, and treatment management in humans. However, the clinical translation of nanoparticle probes, including quantum dots, has not kept pace with the accelerated growth in minimally invasive surgical tools that rely on optical imaging agents. The safety, pharmacokinetics, clearance properties, and radiation dosimetry of (124)I-cRGDY-PEG-C dots were assessed by serial PET and computerized tomography after intravenous administration in patients. Metabolic profiles and laboratory tests of blood and urine specimens, obtained before and after particle injection, were monitored over a 2-week interval. Findings are consistent with a well-tolerated inorganic particle tracer exhibiting in vivo stability and distinct, reproducible pharmacokinetic signatures defined by renal excretion. No toxic or adverse events attributable to the particles were observed. Coupled with preferential uptake and localization of the probe at sites of disease, these first-in-human results suggest safe use of these particles in human cancer diagnostics.
    No preview · Article · Oct 2014 · Science translational medicine
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    ABSTRACT: Because of their chemical properties and multiday half lives, iodine-124 and zirconium-89 are being used in a growing number of PET imaging studies. Some aspects of their quantitation, however, still need attention. For 89Zr the PET images should, in principle, be as quantitatively accurate as similarly reconstructed 18F measurements. We found, however, that images of a 20 cm well calibration phantom containing 89Zr underestimated the activity by approximately 10% relative to a dose calibrator measurement (Capintec CRC-15R) using a published calibration setting number of 465. PET images of 124I, in contrast, are complicated by the contribution of decays in cascade that add spurious coincident events to the PET data. When these cascade coincidences are properly accounted for, quantitatively accurate images should be possible. We found, however, that even with this correction we still encountered what appeared to be a large variability in the accuracy of the PET images when compared to dose calibrator measurements made using the calibration setting number, 570, recommended by Capintec. We derive new calibration setting numbers for 89Zr and 124I based on their 511 keV photon peaks as measured on an HPGe detector. The peaks were calibrated relative to an 18F standard, the activity level of which was precisely measured in a dose calibrator under well-defined measurement conditions. When measuring 89Zr on a Capintec CRC-15R we propose the use of calibration setting number 517. And for 124I, we recommend the use of a copper filter surrounding the sample and the use of calibration setting number 494. The new dose calibrator measurement procedures we propose will result in more consistent and accurate radioactivity measurements of 89Zr and 124I. These and other positron emitting radionuclides can be accurately calibrated relative to 18F based on measurements of their 511 keV peaks and knowledge of their relative positron abundances.
    Full-text · Article · Sep 2014 · PLoS ONE

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Purpose: To assess and account for the impact of respiratory motion on the variability of activity and volume determination of liver tumor in positron emission tomography (PET) through a comparison between free-breathing (FB) and respiration-suspended (RS) PET images. Methods: As part of a PET/computed tomography (CT) guided percutaneous liver ablation procedure performed on a PET/CT scanner, a patient's breathing is suspended on a ventilator, allowing the acquisition of a near-motionless PET and CT reference images of the liver. In this study, baseline RS and FB PET/CT images of 20 patients undergoing thermal ablation were acquired. The RS PET provides near-motionless reference in a human study, and thereby allows a quantitative evaluation of the effect of respiratory motion on PET images obtained under FB conditions. Two methods were applied to calculate tumor activity and volume: (1) threshold-based segmentation (TBS), estimating the total lesion glycolysis (TLG) and the segmented volume and (2) histogram-based estimation (HBE), yielding the background-subtracted lesion (BSL) activity and associated volume. The TBS method employs 50% of the maximum standardized uptake value (SUVmax) as the threshold for tumors with SUVmax≥2× SUVliver-bkg, and tumor activity above this threshold yields TLG50%. The HBE method determines local PET background based on a Gaussian fit of the low SUV peak in a SUV-volume histogram, which is generated within a user-defined and optimized volume of interest containing both local background and lesion uptakes. Voxels with PET intensity above the fitted background were considered to have originated from the tumor and used to calculate the BSL activity and its associated lesion volume. Results: Respiratory motion caused SUVmax to decrease from RS to FB by -15%±11% (p=0.01). Using TBS method, there was also a decrease in SUVmean (-18%±9%, p=0.01), but an increase in TLG50% (18%±36%) and in the segmented volume (47%±52%, p=0.01) from RS to FB PET images. The background uptake in normal liver was stable, 1%±9%. In contrast, using the HBE method, the differences in both BSL activity and BSL volume from RS to FB were -8%±10% (p=0.005) and 0%±16% (p=0.94), respectively. Conclusions: This is the first time that almost motion-free PET images of the human liver were acquired and compared to free-breathing PET. The BSL method's results are more consistent, for the calculation of both tumor activity and volume in RS and FB PET images, than those using conventional TBS. This suggests that the BSL method might be less sensitive to motion blurring and provides an improved estimation of tumor activity and volume in the presence of respiratory motion.
    Full-text · Article · Sep 2014 · Medical Physics
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    ABSTRACT: Introduction The increasing use of molecular imaging probes as biomarkers in oncology emphasizes the need for robust and stable methods for quantifying tracer uptake in PET imaging. The primary motivation for this research was to find an accurate method to quantify the total tumor uptake. Therefore we developed a histogram-based method to calculate the background subtracted lesion (BSL) activity and validated BSL by comparing the quantitative consistency with the total lesion glycolysis (TLG) in phantom and patient studies. Methods A thorax phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was calculated with a fixed threshold at SUV 2.5 (TLG2.5) and a relative threshold at 42% of SUVmax (TLG42%). The histogram for each VOI was built and BSL was calculated. Comparison with the total injected FDG activity (TIA) was performed using concordance correlation coefficients (CCC) and the slope (a). Fifty consecutive patients with FDG-avid lung tumors were selected under an IRB waiver. TLG42%, TLG2.5 and BSL were compared to the reference standard calculating CCC and the slope. Results In both phantoms, the CCC for lesions with a TIA ≤ 50 ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC = 0.933, a = 1.189), than for TLG42% (CCC = 0.350, a = 0.731) or TLG2.5 (CCC = 0.761, a = 0.727). In 50 lung lesions BSL had a slope closer to 1 compared to the reference activity than TLG42% (a = 1.084 vs 0.618 - for high activity lesions) and also closer to 1 than TLG2.5 (a = 1.117 vs 0.548 - for low activity lesions). Conclusion The histogram based BSL correlated better with TIA in both phantom studies than TLG2.5 or TLG42%. Also in lung tumors, the BSL activity is overall more accurate in quantifying the lesion activity compared to the two most commonly applied TLG quantification methods.
    No preview · Article · May 2014 · Nuclear Medicine and Biology
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    ABSTRACT: The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (RaCl2), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered Ra dichloride were typically less than 2 μSv h MBq on contact and averaged 0.02 μSv h MBq at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5-11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that Ra may provide a new standard of care for patients with CRPC and bone metastases.
    No preview · Article · Apr 2014 · Health physics
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    ABSTRACT: Reasons for failure in prior human glioma convection-enhanced delivery (CED) clinical trials remain unclear. Concentration-dependent volume of distribution (Vd) measurement of CED-infused agents in the human brain is challenging and highlights a potential technical shortcoming. Activity of iodine isotope 124 ((124)I ) in tissue can be directly measured in vivo with high resolution via PET. With the potential therapeutic utility of radioimmunotherapy, we postulate (124)I conjugated to the antiglioma monoclonal antibody 8H9 may serve as a "theragnostic" agent delivered via CED to diffuse intrinsic pontine glioma. Fifteen rats underwent CED of 0.1-1.0 mCi of (131)I-8H9 to the pons for toxicity evaluation. Six additional rats underwent CED of 10 µCi of (124)I-8H9 to the pons for dosimetry, with serial microPET performed for 1 week. Two primates underwent CED of gadolinium-albumin and 1.0 mCi of (124)I-8H9 to the pons for safety and dosimetry analysis. Serial postoperative PET, blood, and CSF radioactivity counts were performed. One rat (1.0 mCi (131)I-8H9 infusion) suffered toxicity necessitating early sacrifice. PET analysis in rats yielded a pontine absorbed dose of 37 Gy/mCi. In primates, no toxicity was observed, and absorbed pontine dose was 3.8 Gy/mCi. Activity decreased 10-fold with 48 h following CED in both animal models. Mean Vd was 0.14 cc(3) (volume of infusion [Vi] to Vd ratio = 14) in the rat and 6.2 cc(3) (Vd/Vi = 9.5) in primate. The safety and feasibility of (124)I dosimetry following CED via PET is demonstrated, establishing a preclinical framework for a trial evaluating CED of (124)I-8H9 for diffuse intrinsic pontine glioma.
    Full-text · Article · Feb 2014 · Neuro-Oncology

  • No preview · Conference Paper · Feb 2014
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    ABSTRACT: Many common PET segmentation methods for malignant lesions use surrounding background activity as a reference. To date, background has to be measured by drawing a second volume of interest (VOI) in nearby, undiseased tissue. This is time consuming as two VOIs have to be determined for each lesion. The aim of our study was to analyse whether background activity in different organs and body regions could be calculated from the tumour VOI by histogram analyses. The institutional review board waived informed consent for this retrospective study. For each of the following tumour types and areas - head and neck (neck), lung, hepatic metastasis (liver), melanoma (skin), and cervix (pelvis) - 10 consecutive patients with biopsy-proven tumours who underwent F-fluorodeoxyglucose-PET in January 2012 were retrospectively selected. One lesion was selected and two readers drew a cubical VOI around the lesion (VOItumour) and over the background (VOIBG). The mean value of VOIBG was compared with the mode of the histogram, using equivalence testing with an equivalence margin of ±0.5 SUV. Inter-reader agreement was analysed for the mean background, and the mode of the VOItumour histogram was assessed using the concordance correlation coefficient. For both readers, the mode of VOItumour was equivalent to the mean of VOIBG (P<0.0001 for R1 and R2). The inter-reader agreement was almost perfect, with a concordance correlation coefficient of greater than 0.92 for both the mode of VOItumour and the mean of VOIBG. Background activity determined within a tumour VOI using histogram analysis is equivalent to separately measured mean background values, with an almost perfect inter-reader agreement. This could facilitate PET quantification methods based on background values without increasing workload.
    Preview · Article · Nov 2013 · Nuclear Medicine Communications

Publication Stats

10k Citations
895.93 Total Impact Points


  • 1993-2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medical Physics
      • • Department of Nuclear Medicine
      • • Department of Neurology
      • • Gynecology Service
      New York, New York, United States
  • 2012
    • Duke University
      Durham, North Carolina, United States
  • 2002
    • Cornell University
      Итак, New York, United States
  • 2001
    • CUNY Graduate Center
      New York, New York, United States
  • 1997
    • New York Medical College
      • Department of Pathology
      New York, New York, United States
  • 1993-1994
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 1990-1994
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, Massachusetts, United States