John L Humm

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

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Publications (229)890.42 Total impact

  • Sean Carlin, John Humm
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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.
  • Journal of Vascular and Interventional Radiology 02/2015; 26(2):S59. DOI:10.1016/j.jvir.2014.12.162 · 2.15 Impact Factor
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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.
    Science translational medicine 10/2014; 6(260):260ra149. DOI:10.1126/scitranslmed.3009524 · 14.41 Impact Factor
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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.
    PLoS ONE 09/2014; 9(9):e106868. DOI:10.1371/journal.pone.0106868 · 3.53 Impact Factor
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    ABSTRACT: 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.
    Medical Physics 09/2014; 41(9):091905. DOI:10.1118/1.4892602 · 3.01 Impact Factor
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    ABSTRACT: Purpose: To investigate the performance of a new penalized-likelihood PET image reconstruction algorithm using the 11-norm total-variation (TV) sum of the 1st through 4th-order gradients as the penalty. Simulated and brain patient data sets were analyzed.
    Medical Physics 06/2014; 41(6):438-438. DOI:10.1118/1.4889209 · 3.01 Impact Factor
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    ABSTRACT: Purpose: This study demonstrates a methodology for tracking changes in metastatic bone disease using trajectories in material basis space in serial dual energy computed tomography (DECT) studies.
    Medical Physics 06/2014; 41(6):451-451. DOI:10.1118/1.4889254 · 3.01 Impact Factor
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    ABSTRACT: Purpose: To develop a procedure for accurate determination of PET tracer concentration with high spatial accuracy in situ by performing Quantitative Autoradiography of Biopsy Specimens (QABS) extracted under PET/CT guidance.
    Medical Physics 06/2014; 41(6):439-439. DOI:10.1118/1.4889211 · 3.01 Impact Factor
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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.
    Nuclear Medicine and Biology 05/2014; DOI:10.1016/j.nucmedbio.2014.02.006 · 2.41 Impact Factor
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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.
    Health physics 04/2014; 106(4):494-504. DOI:10.1097/HP.0b013e3182a82b37 · 0.92 Impact Factor
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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.
    Neuro-Oncology 02/2014; DOI:10.1093/neuonc/not298 · 5.29 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 02/2014; 88(2):474. DOI:10.1016/j.ijrobp.2013.11.044 · 4.18 Impact Factor
  • European journal of nuclear medicine and molecular imaging 01/2014; 41(suppl 2):S367-S367. · 5.22 Impact Factor
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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.
    Nuclear Medicine Communications 11/2013; DOI:10.1097/MNM.0000000000000045 · 1.37 Impact Factor
  • John L Humm, Hooshang Nikjoo
    Radiation Research 11/2013; 180(5):553-555. DOI:10.1667/RR00DC.1 · 2.70 Impact Factor
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    ABSTRACT: The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate (18)F-FES PET and ER expression in patients with primary, operable breast cancer. Forty-eight patients were prospectively enrolled in an institutional review board-approved protocol and signed an informed consent form. All patients had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and PgR percentage expression (46 surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and progesterone receptor (PgR) was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET uptake using univariate and multivariate analysis. Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty-one patients had nodal involvement. (18)F-FES PET identified 5 patients with axillary nodal uptake (median SUV, 3.0; range, 1.7-6.9). These 5 patients had ER-positive breast cancer, and all had more than 4 positive nodes at the time of axillary node dissection. (18)F-FES PET SUV was associated with immunohistochemistry ER expression. The sensitivity and specificity of the (18)F-FES PET for the breast lesion were 0.85 and 0.75, respectively. Estrogen and progesterone gene expression (ESR1, ESR2, and PGR) was not associated with (18)F-FES PET SUV (Spearman rank correlation). We found a significant correlation between (18)F-FES PET SUV and tumor size (P = 0.0015) but not with ductal histology, grade, HER2-neu overexpression, PgR, estradiol, BMI, or lean BMI (logistic regression). ER expression (P < 0.001) and tumor size (P < 0.0001) were significant on multivariate regression analysis. (18)F-FES PET SUV correlated with ER immunohistochemistry expression but not gene expression in our patients with early breast cancer. We found that size of primary tumor was significantly associated with (18)F-FES PET SUV. (18)F-FES PET is highly predictive for metastatic disease and helped in the identification of patients with metastatic disease in a preoperative setting.
    Journal of Nuclear Medicine 08/2013; 54(10). DOI:10.2967/jnumed.112.113373 · 5.56 Impact Factor
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    ABSTRACT: BACKGROUND: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. METHODS: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. RESULTS: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. CONCLUSIONS: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients.Trial registration: ClinicalTrials.gov NCT00588276.
    06/2013; 3(1):42. DOI:10.1186/2191-219X-3-42
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    ABSTRACT: Purpose: To determine the effect of respiratory motion on liver tumor volume by FDG PET. Methods: PET/CT was performed on patients during free breathing (FB) and then breath hold (BH) by suspending respiration on a ventilator, allowing 2–3 minutes of near‐motionless PET data to be acquired. A reference region on normal liver was selected as a control for background FDG uptake quantification. A dataset of 11 patients with 13 liver lesions were studied under both BH and FB conditions before tumor ablation. A threshold‐based segmentation method (GE Advantage) and a background subtraction classification method (in‐house) were used to delineate FDG tumor volumes under FB and BH conditions. For tumors with an SUVmax>2×SUV(liver‐bkg), a threshold of 50% of the maximum uptake was used for segmentation via the GE Advantage PET VCAR software module. The background‐subtracted lesion (BSL) method was implemented by a Gaussian fit of the background from the SUV‐volume histogram (SVH). A cutoff threshold was defined as twice sigma of the Gaussian fit plus the mean. Subtraction of this Gaussian fit from the SVH beyond this cutoff determines the signal above background. Custom software was developed for BSL classification. Pixels with PET intensity above the fitted background were calculated as the tumor volume. Results: In BH PET images, there was an increase in SUVmax [16%(σ=11%)] and SUVmean [20%(σ=9%)], but a reduction in delineated volume [57%(σ=55%)], in comparison with FB PET images. The background uptake in normal liver showed no bias, with an average of −1%(σ=10%). The BSL values are similar between BH and FB for high‐intensity lesions (SUVmax>9 g/ml). Conclusion: This is the first time that a motion‐free PET image of the liver was acquired in patients and compared with free‐breathing results. Motion blurring caused an apparent volume increase of 50% on average with 16%–20% reductions in SUVmax and SUVmean.
    Medical Physics 06/2013; 40(6-6). DOI:10.1118/1.4814019 · 3.01 Impact Factor
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    ABSTRACT: Purpose: Current commercially available small animal irradiators provide limited software tools for treatment planning. We report on the implementation of an in‐house treatment planning system, Metropolis, for micro‐irradiator and compare its capabilities with those of the vendor‐supplied system, TPS(XRAD). Methods: The 225 kV beam of the micro‐irradiator was commissioned using both ion chamber and radiographic film (EBT3). Dose calculation in Metropolis was verified by comparing with measured dose in phantom. Starting from a 3D CT image of a tumor‐bearing mouse, the same treatment plans were designed in the two systems. In TPS(XRAD), a treatment point was selected on a CT slice, two orthogonal beams were defined based on tumor size on the CT slice, and isocenter depth was computed from a body contour determined by image thresholding. In Metropolis, structures (outer, tumor, and lung) were contoured on CT images, beams were defined based on tumor volume coverage on beams‐eye‐view (BEV), 3D dose calculation was performed, and plan was evaluated based on dose distribution and dose‐volume histogram (DVH). Results: Measured dose in phantom agreed with Metropolis calculation within 3% for all collimators. The beam‐on‐times calculated by the two systems agreed within 1% at isocenter. Whereas TPS(XRAD) provides only beam‐on‐time for each beam, Metropolis capabilities include various image segmentation tools, multimodality image registration, verification of target coverage and normal tissue sparing using BEV, 3D isodose distribution overlaid on CT images, and DVH. DVH inspection of the two‐beam treatment plan reveals a tumor dose variation (D95 : 388 and D05 : 401 cGy) and dose to lung (Dmean: 84 cGy) for a prescribed isocenter dose of 400 cGy. Conclusion: By implementing a clinical TPS for a small animal irradiator system, both efficient planning and precise plan evaluation become possible, allowing the full potential of advanced micro‐irradiator radiation treatment planning to be conducted for pre‐clinical experimentation.
    Medical Physics 06/2013; 40(6):115. DOI:10.1118/1.4814061 · 3.01 Impact Factor

Publication Stats

8k Citations
890.42 Total Impact Points

Institutions

  • 1994–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medical Physics
      • • Department of Nuclear Medicine
      • • Department of Medicine
      • • Gynecology Service
      New York, New York, United States
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2000
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 1997
    • New York Medical College
      • Department of Pathology
      New York, New York, United States
  • 1990–1993
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, Massachusetts, United States