John L Humm

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

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Publications (217)835.96 Total impact

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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. · 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. · 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. · 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; · 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. · 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; · 5.29 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; · 1.37 Impact Factor
  • John L Humm, Hooshang Nikjoo
    Radiation Research 11/2013; 180(5):553-555. · 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; · 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.
    EJNMMI research. 06/2013; 3(1):42.
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    ABSTRACT: PURPOSE: (223)Ra-Dichloride ((223)Ra) is a novel bone-seeking alpha-emitter that prolongs survival in patients with castration-resistant metastatic prostate cancer. We conducted a study to better profile the pharmacokinetics, pharmacodynamics, and biodistribution of this agent. METHODS: Ten patients received either 50, 100, or 200 kBq of (223)Ra per kilogram of body weight. Subsequently, six of these ten patients received a second dose of 50 kBq/kg. Pharmacokinetics and biodistribution were assessed by serial blood sampling, planar imaging, and whole-body counting. Pharmacodynamic assessment was based on measurements of prostate-specific antigen, bone alkaline phosphatase, and serum N-telopeptide. Safety was also assessed. RESULTS: Pharmacokinetic studies showed rapid clearance of (223)Ra from the vasculature, with a median of 14 % (range 9-34 %), 2 % (range 1.6-3.9 %), and 0.5 % (range 0.4-1.0 %) remaining in plasma at the end of infusion, after 4 h, and after 24 h, respectively. Biodistribution studies showed early passage into the small bowel and subsequent fecal excretion with a median of 52 % of administered (223)Ra in the bowel at 24 h. Urinary excretion was relatively minor (median of 4 % of administered (223)Ra). Bone retention was prolonged. No dose-limiting toxicity was observed. Pharmacodynamic effects were observed (alkaline phosphatase and serum N-telopeptides) in a significant fraction of patients. CONCLUSION: (223)Ra cleared rapidly from plasma and rapidly transited into small bowel, with fecal excretion the major route of elimination. Administered activities up to 200 kBq/kg were associated with few side effects and appeared to induce a decline in serum indicators of bone turnover.
    European Journal of Nuclear Medicine 05/2013; · 4.53 Impact Factor
  • Med Phys. 01/2013; 40(6).
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    ABSTRACT: Purpose: To generate parametric images of tumor hypoxia in a tumor-bearing rat model using voxel-based compart- mental analysis of dynamic fluorine-18 labeled misonidazole (18F-FMISO) microPET™ images, and to compare the parametric images thus derived with static “late” 18F-FMISO microPET™ images for the detection of tumor hypoxia. Materials and Methods: Nude rats bearing HT-29 colorectal carcinoma xenografts (≈1.5 - 2 cm in diameter) in the right hind limb were positioned in a custom-fabricated, animal-specific foam mold. Animals were injected via the tail vein with ≈55.5 MBq 18F-FMISO and continuously imaged for either 60 or 120 minutes, with additional late static im- ages up to 3 hour post-injection. The raw list-mode data was reconstructed into 37 - 64 frames with earlier frames of shorter time durations (12 - 15 seconds) and later frames of longer durations (up to 300 seconds). Time activity curves (TACs) were generated over regions encompassing the tumor as well as an artery, the latter for use as an input function. A beta version of a compartmental modeling package (BioGuide™, Philips Healthcare) was used to generate parametric images of k3 and Ki, rate constants of entrapment and flux of 18F-FMISO, respectively. Results: Data for 7 HT-29 tumor xenografts were presented, 6 of which yielded clear areas of tumor hypoxia as defined by Ki/k3 maps. Importantly, intra- tumoral foci with high 18F-FMISO uptakes on the late images did not always exhibit high Ki/k3 values and may there- fore represent false-positives for radiobiologically significant hypoxia. Conclusions: This study attempts to quantify tumor hypoxia using compartmental analysis of dynamic 18F-FMISO PET images in rodent xenograft tumor models. The results demonstrate feasibility of the approach in small-animal imaging studies, and provide evidence for the possi-ble unreliability of late-time static imaging of 18F-FMISO PET in identifying tumor hypoxia.
    International Journal of Medical Physics, Clinical Engineering and Radiation Oncology. 11/2012; 1(3):95-104.
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    ABSTRACT: Purpose: Patient exposure rate measurements verify published patient dose rate data and characterize dose rates near 2-18-fluorodeoxyglucose ((18)F-FDG) patients. A specific dose rate constant based on patient exposure rate measurements is a convenient quantity that can be applied to the desired distance, injection activity, and time postinjection to obtain an accurate calculation of cumulative external radiation dose. This study reports exposure rates measured at various locations near positron emission tomography (PET) (18)F-FDG patients prior to PET scanning. These measurements are normalized for the amount of administered activity, measurement distance, and time postinjection and are compared with other published data.Methods: Exposure rates were measured using a calibrated ionization chamber at various body locations from 152 adult oncology patients postvoid after a mean uptake time of 76 min following injection with a mean activity of 490 MBq (18)F-FDG. Data were obtained at nine measurement locations for each patient: three near the head, four near the chest, and two near the feet.Results: On contact with, 30 cm superior to and 30 cm lateral to the head, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.482 (0.511), 0.135 (0.155), and 0.193 (0.223) μSv∕MBq h, respectively. On contact with, 30 cm anterior to, 30 cm lateral to and 1 m anterior to the chest, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.623 (0.709), 0.254 (0.283), 0.190 (0.218), and 0.067 (0.081) μSv∕MBq h respectively. 30 cm inferior and 30 cm lateral to the feet, the mean (75th percentile) dose rates per unit injected activity at 60 min postinjection were 0.024 (0.022) and 0.039 (0.044) μSv∕MBq h, respectively.Conclusions: The measurements for this study support the use of 0.092 μSv m(2)∕MBq h as a reasonable representation of the dose rate anterior from the chest of patients immediately following injection. This value can then be reliably scaled to the desired time and distance for planning and staff dose evaluation purposes. At distances closer than 1 m, a distance-specific dose rate constant of 0.367 μSv∕MBq h at 30 cm is recommended for accurate calculations. An accurate patient-specific dose rate constant that accounts for patient-specific variables (e.g., distribution and attenuation) will allow an accurate evaluation of the dose rate from a patient injected with an isotope rather than simply utilizing a physical constant.
    Medical Physics 10/2012; 39(10):6071-9. · 3.01 Impact Factor
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    ABSTRACT: (18)F-fluoromisonidazole PET, a noninvasive means of identifying hypoxia in tumors, has been widely applied but with mixed results, raising concerns about its accuracy. The objective of this study was to determine whether kinetic analysis of dynamic (18)F-fluoromisonidazole data provides better discrimination of tumor hypoxia than methods based on a simple tissue-to-plasma ratio. Eleven Dunning R3327-AT prostate tumor-bearing nude rats were immobilized in custom-fabricated whole-body molds, injected intravenously with (18)F-fluoromisonidazole, and imaged dynamically for 105 min. They were then transferred to a robotic system for image-guided measurement of intratumoral partial pressure of oxygen (Po(2)). The dynamic (18)F-fluoromisonidazole uptake data were fitted with 2 variants of a 2-compartment, 3-rate-constant model, one constrained to have K(1) equal to k(2) and the other unconstrained. Parametric images of the rate constants were generated. The Po(2) measurements were compared with spatially registered maps of kinetic rate constants and tumor-to-plasma ratios. The constrained pharmacokinetic model variant was shown to provide fits similar to that of the unconstrained model and did not introduce significant bias in the results. The trapping rate constant, k(3), of the constrained model provided a better discrimination of low Po(2) than the tissue-to-plasma ratio or the k(3) of the unconstrained model. The use of kinetic modeling on a voxelwise basis can identify tumor hypoxia with improved accuracy over simple tumor-to-plasma ratios. An effective means of controlling noise in the trapping rate constant, k(3), without introducing significant bias, is to constrain K(1) equal to k(2) during the fitting process.
    Journal of Nuclear Medicine 08/2012; 53(10):1608-15. · 5.56 Impact Factor
  • Sean Carlin, John L Humm
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    ABSTRACT: In the past 25 y, a large amount of clinical experience with hypoxia PET tracers has accumulated. This article discusses recent improvements in image acquisition protocols and tracer pharmacology that have resulted in improved understanding of the underlying physiologic processes. The widespread clinical adoption of hypoxia PET tracers will depend largely on their utility in treatment prescription and in outcome monitoring. The establishment and validation of hypoxia-directed treatment protocols are still under development, and it is envisaged that the design and use of future hypoxia PET tracers will develop as part of this process.
    Journal of Nuclear Medicine 07/2012; 53(8):1171-4. · 5.56 Impact Factor
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    ABSTRACT: The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. (64)Cu-ATSM was administered during dynamic PET imaging, and temporal changes in (64)Cu-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conducted by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K(i)) constant was 12-fold that of muscle, whereas the distribution volume (V(d)) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in (64)Cu-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of (64)Cu-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was (64)Cu-ATSM and Hoechst-33342. The oxygen partial pressures at which (64)Cu-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown (64)Cu-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer.
    International journal of radiation oncology, biology, physics 06/2012; 84(3):e393-9. · 4.59 Impact Factor
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    ABSTRACT: The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images.
    Seminars in nuclear medicine 05/2012; 42(3):208-18. · 3.96 Impact Factor
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    ABSTRACT: Bone marrow is usually dose-limiting for radioimmunotherapy. In this study, we directly estimated red marrow activity concentration and the self-dose component of absorbed radiation dose to red marrow based on PET/CT of 2 different (124)I-labeled antibodies (cG250 and huA33) and compared the results with plasma activity concentration and plasma-based dose estimates. Two groups of patients injected with (124)I-labeled monoclonal antibodies (11 patients with renal cancer receiving (124)I-cG250 and 5 patients with colorectal cancer receiving (124)I- huA33) were imaged by PET or PET/CT on 2 or 3 occasions after infusion. Regions of interest were drawn over several lumbar vertebrae, and red marrow activity concentration was quantified. Plasma activity concentration was also quantified using multiple patient blood samples. The red marrow-to-plasma activity concentration ratio (RMPR) was calculated at the times of imaging. The self-dose component of the absorbed radiation dose to the red marrow was estimated from the images, from the plasma measurements, and using a combination of both sets of measurements. RMPR was observed to increase with time for both groups of patients. Mean (±SD) time-dependent RMPR (RMPR(t)) for the cG250 group increased from 0.13 ± 0.06 immediately after infusion to 0.23 ± 0.09 at approximately 6 d after infusion. For the huA33 group, mean RMPR(t) was 0.10 ± 0.04 immediately after infusion, 0.13 ± 0.05 approximately 2 d after infusion, and 0.20 ± 0.09 approximately 7 d after infusion. Plasma-based estimates of red marrow self-dose tended to be greater than image-based values by, on average, 11% and 47% for cG250 and huA33, respectively, but by as much as -73% to 62% for individual patients. The hybrid method combining RMPR(t) and plasma activity concentration provided a closer match to the image-based dose estimates (average discrepancies, -2% and 18% for cG250 and huA33, respectively). These results suggest that the assumption of time-independent proportionality between red marrow and plasma activity concentration may be too simplistic. Individualized imaged-based dosimetry is probably required for the optimal therapeutic delivery of radiolabeled antibodies, which does not compromise red marrow and may allow, for some patients, a substantial increase in administered activity and thus tumor dose.
    Journal of Nuclear Medicine 03/2012; 53(4):615-21. · 5.56 Impact Factor
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    ABSTRACT: Molecular imaging is an evolving science that is concerned with the development of novel imaging probes and biomarkers that can be used to non-invasively image molecular and cellular processes. This special issue approaches molecular imaging in the context of radiation research, focusing on biomarkers and imaging methods that provide measurable signals that can assist in the quantification of radiation-induced effects of living systems at the physical, chemical and biological levels. The potential to image molecular changes in response to a radiation insult opens new and exciting opportunities for a more profound understanding of radiation biology, with the possibility of translation of these techniques to radiotherapy practice. This special issue brings together 14 reviews dedicated to the use of molecular imaging in the field of radiation research. The initial three reviews are introductory overviews of the key molecular imaging modalities: magnetic resonance, nuclear and optical. This is followed by 11 reviews each focusing on a specialist area within the field of radiation research. These include: hypoxia and perfusion, tissue metabolism, normal tissue injury, cell death and viability, receptor targeting and nanotechnology, reporter genes, reactive oxygen species (ROS), and biological dosimetry. Over the preceding decade, molecular imaging brought significant new advances to our understanding of every area of radiation biology. This special issue shows us these advances and points to the vibrant future of our field armed with these new capabilities.
    Radiation Research 02/2012; 177(4):329-30. · 2.70 Impact Factor

Publication Stats

7k Citations
835.96 Total Impact Points

Institutions

  • 1994–2014
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medical Physics
      • • Department of Neurology
      • • Department of Radiation Oncology
      • • Department of Radiology
      • • Department of Pediatrics
      • • Department of Medicine
      • • Gynecology Service
      New York City, New York, United States
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
    • Brigham and Women's Hospital
      • Center for Brain Mind Medicine
      Boston, MA, United States
  • 2010
    • Virginia Commonwealth University
      • Department of Radiation Oncology
      Richmond, VA, United States
  • 2008
    • Loyola University Medical Center
      • Department of Radiation Oncology
      Maywood, Illinois, United States
  • 2000
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 1990–1994
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, MA, United States
  • 1988–1989
    • Concordia University Montreal
      • Department of Physics
      Montréal, Quebec, Canada