Search tips
Search criteria

Results 1-13 (13)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Molecular Imaging of Pulmonary Cancer and Inflammation 
Molecular imaging (MI) may be defined as imaging in vivo using molecules that report on biologic function. This review will focus on the clinical use of radioactive tracers (nonpharmacologic amounts of compounds labeled with a radioactive substance) that permit external imaging using single photon emission computed tomography (planar, SPECT) or positron emission tomography (PET) imaging. Imaging of lung cancer has been revolutionized with the use of fluorine-18–labeled fluorodeoxyglucose (18F-FDG), an analog of glucose that can be imaged using PET. The ability to carry out whole body imaging after intravenous injection of 18F-FDG allows accurate staging of disease, helping to determine regional and distant nodal and other parenchymal involvement. Glycolysis is increased in nonmalignant conditions, including inflammation (e.g., sarcoidosis), and 18F-FDG PET is a sensitive method for evaluation of active inflammatory disease. Inflammatory disease has been imaged, even before the advent of PET, with planar and SPECT imaging using gallium-67, a radiometal that binds to transferrin. Metabolic alteration in pulmonary pathology is currently being studied, largely in lung cancer, primarily with PET, with a variety of other radiotracers. Prominent among these is thymidine; fluorine-18–labeled thymidine PET is being increasingly used to evaluate proliferation rate in lung and other cancers. This overview will focus on the clinical utility of 18F-FDG PET in the staging and therapy evaluation of lung cancer as well as in imaging of nonmalignant pulmonary conditions. PET and SPECT imaging with other radiotracers of interest will also be reviewed. Future directions in PET imaging of pulmonary pathophysiology will also be explored.
PMCID: PMC3266015  PMID: 19687220
SPECT; PET; radiolabeled ligands; cancer; infection
2.  Development of 124I-Immuno-PET Targeting Tumor Vascular TEM1/Endosialin 
Tumor endothelial marker 1 (TEM1/endosialin) is a tumor vascular marker highly overexpressed in multiple human cancers with minimal expression in normal adult tissue. In this study, we report the preparation and evaluation of 124I-MORAb-004, a 124I-labeled humanized monoclonal antibody targeting an extracellular epitope of human TEM1 (hTEM1), for its ability to specifically and sensitively detect vascular cells expressing hTEM1 in vivo.
MAb MORAb-004 was directly iodinated with 125I and 124I, and in vitro binding and internalization parameters were characterized. The in vivo behavior of radioiodinated-MORAb-004 was characterized in mice bearing subcutaneous ID8 tumors enriched with mouse endothelial cells expressing hTEM1, or control tumors, by biodistribution studies and small animal immuno-PET studies.
MORAb-004 was radiolabeled with high efficiency and isolated in high purity. In vitro studies demonstrated specific and sensitive binding of MORAb-004 to MS1 mouse endothelial cells expressing hTEM1, with no binding to control MS1 cells. 125I-MORAb-004 and 124I MORAb-004 both had an immunoreactivity of approximately 90%. In vivo biodistribution experiments revealed rapid, highly specific and sensitive uptake of MORAb-004 in MS1-TEM1 tumors at 4 h (153.2 ± 22.2 percent of injected dose per gram [%ID/g]), 24 h (127.1 ± 42.9 %ID/g), 48 h (130.3 ± 32.4 %ID/g), 72 h (160.9 ± 32.1 %ID/g), and 6 d (10.7 ± 1.8 %ID/g). Excellent image contrast was observed with 124I-immuno-PET. MORAb-004 uptake was statistically higher in TEM1-positive tumors versus control tumors, as measured by biodistribution and immuno-PET studies. Binding specificity was confirmed by blocking studies using excess nonlabeled MORAb-004.
In our preclinical model, with hTEM1 exclusively expressed on engineered murine endothelial cells that integrate into the tumor vasculature, 124I-MORAb-004 displays high tumor–to–background tissue contrast fordetection of hTEM1 in easily accessible tumor vascular compartments. These studies strongly suggest the clinical utility of 124I-MORAb-004 immunoPET in assessing TEM1 tumor-status.
PMCID: PMC4089496  PMID: 24525208
Immuno-PET; TEM1; Endosialin; MORAb-004; mononclonal antibodies
4.  Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer 
EJNMMI Research  2013;3:42.
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.
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.
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.
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 NCT00588276
PMCID: PMC3686612  PMID: 23731770
Hypoxia; Iodine-124; IAZGP; PET imaging; 2-Nitroimidazole; Radiation dosimetry; Head and neck cancer; Colorectal cancer
6.  124I-huA33 Antibody Uptake Is Driven by A33 Antigen Concentration in Tissues from Colorectal Cancer Patients Imaged by Immuno-PET 
Journal of Nuclear Medicine  2011;52(12):1878-1885.
The primary aim of this analysis was to examine the quantitative features of antibody–antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients.
Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide 124I (124I-huA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination.
PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of 124I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ~0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ~0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%–50%.
The in vivo bio-distribution of 124I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions.
PMCID: PMC3394180  PMID: 22068895
huA33; colorectal cancer; 124I; immuno-PET; radioimmunotherapy
7.  124I-huA33 Antibody PET of Colorectal Cancer 
Journal of Nuclear Medicine  2011;52(8):1173-1180.
Humanized A33 (huA33) is a promising monoclonal antibody that recognizes A33 antigen, which is present in more than 95% of colorectal cancers and in normal bowel. In this study, we took advantage of quantitative PET to evaluate 124I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also determined the biodistribution of 124I-huA33 when a large dose of human intravenous IgG (IVIG) was administered to manipulate the Fc receptor or when 124I-huA33 was given via hepatic arterial infusion (HAI).
We studied 25 patients with primary or metastatic colorectal cancer; 19 patients had surgical exploration or resection. Patients received a median of 343 MBq (44.4–396 MBq) and 10 mg of 124I-huA33. Nineteen patients received the antibody intravenously and 6 patients via HAI, and 5 patients also received IVIG.
Ten of 12 primary tumors were visualized in 11 patients. The median concentration in primary colon tumors was 0.016% injected dose per gram, compared with 0.004% in normal colon. The PET-based median ratio of hepatic tumor uptake to normal-liver uptake was 3.9 (range, 1.8–22.2). Quantitation using PET, compared with well counting of serum and tissue, showed little difference. Prominent uptake in bowel hindered tumor identification in some patients. Pharmacokinetics showed that patients receiving IVIG had a significantly shorter serum half-time (41.6 ± 14.0 h) than those without (65.2 ± 9.8 h). There were no differences in clearance rates among the intravenous group, IVIG group, and HAI group, nor was there any difference in serum area under the curve, maximum serum concentration, or volume of distribution. Weak titers of human–anti-human antibodies were observed in 6 of 25 patients. No acute side effects or significant toxicities were associated with huA33.
Good localization of 124I-huA33 in colorectal cancer with no significant toxicity has been observed. PET-derived 124I concentrations agreed well with those obtained by well counting of surgically resected tissue and blood, confirming the quantitative accuracy of 124I-huA33 PET. The HAI route had no advantage over the intravenous route. No clinically significant changes in blood clearance were induced by IVIG.
PMCID: PMC3394182  PMID: 21764796
A33; 124I; antibody; arterial; positron; colon
8.  Bone Marrow Dosimetry Using 124I-PET 
Journal of Nuclear Medicine  2012;53(4):615-621.
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 124I-labeled antibodies (cG250 and huA33) and compared the results with plasma activity concentration and plasma-based dose estimates.
Two groups of patients injected with 124I-labeled monoclonal antibodies (11 patients with renal cancer receiving 124I-cG250 and 5 patients with colorectal cancer receiving 124I- 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.
PMCID: PMC3390781  PMID: 22414633
dosimetry; marrow; PET
9.  Sequential Cytarabine and Alpha-Particle Immunotherapy with Bismuth-213-Lintuzumab (HuM195) for Acute Myeloid Leukemia 
Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the antibody’s potency without the nonspecific cytotoxicity associated with β-emitters, the α particle-emitting radionuclide bismuth-213 (213Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of 213Bi-lintuzumab, the first targeted α-emitter, after partially cytoreductive chemotherapy.
Experimental Design
Thirty-one patients with newly diagnosed (n = 13) or relapsed/refractory (n = 18) AML (median age, 67 years; range, 37–80) were treated with cytarabine 200 mg/m2/day for 5 days followed by 213Bi-lintuzumab 18.5–46.25 MBq/kg.
The MTD of 213Bi-lintuzumab was 37 MB/kg; myelosuppression lasting > 35 days was dose-limiting. Extramedullary toxicities were primarily limited to ≤ grade 2 events, including infusion-related reactions. Transient grade 3/4 liver function abnormalities were seen in 5 patients (16%). Treatment-related deaths occurred in 2 of 21 patients (10%) who received the MTD. Significant reductions in marrow blasts were seen at all dose levels. The median response duration was 6 months (range, 2–12). Biodistribution and pharmacokinetic studies suggested that saturation of available CD33 sites by 213Bi-lintuzumab was achieved after partial cytoreduction with cytarabine.
Sequential administration of cytarabine and 213Bi-lintuzumab is tolerable and can produce remissions in patients with AML.
PMCID: PMC2970691  PMID: 20858843
Radioimmunotherapy; Alpha-particles; Acute myeloid leukemia; Monoclonal Antibodies; Bismuth-213
12.  Phase I Study of Samarium-153 Lexidronam With Docetaxel in Castration-Resistant Metastatic Prostate Cancer 
Journal of Clinical Oncology  2009;27(15):2436-2442.
Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 (153Sm) lexidronam.
Patients and Methods
Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m2 and 153Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and 153Sm-EDTMP was administered on day −1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression.
Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of 153Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 153Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption.
Docetaxel and 153Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.
PMCID: PMC2684850  PMID: 19364960
13.  Antibody mass escalation study in patients with castration resistant prostate cancer using 111I-J591: Lesion detectability and dosimetric projections for 90Y radioimmunotherapy 
J591, a monoclonal antibody that targets the external domain of the prostate specific membrane antigen (PSMA), has potential as an agent for radioimmunotherapy. A pilot trial was carried out in patients with prostate cancer using repetitive administrations of escalating masses of J591. An analysis was carried out to assess (1) lesion detectability by 111InJ591 gamma camera imaging compared to standard imaging methods and (2) the effect of increasing antibody mass on lesion detectability, biodistribution and dosimetry.
Fourteen patients with metastatic prostate cancer received escalating amounts (10, 25, 50 and 100 mg) of J591 in a series of administrations each separated by 3 weeks. All antibody administrations included a fixed amount of radiolabeled antibody 111In-DOTA-J591 (2mg of J591 labeled with 185MBq (5 mCi) of 111In via the chelating agent DOTA). Three whole body gamma camera scans with at least one SPECT scan together with multiple whole body count-rate measurements and serum activity concentration measurements were obtained in all patients. Images were analyzed for distribution and lesion targeting. Estimates of clearance rates and liver and lesion uptake were made for each treatment cycle. These estimates were used to generate dosimetric projections for radioimmunotherapy with 90Y-labeled J591.
A total of 80 lesions in 14 patients were detected. Both skeletal and soft tissue disease was targeted by the antibody as seen on 111In-J591 scans. Antibody localized to 93.7% of skeletal lesions detected by conventional imaging. Clearance of radioactivity from whole body, serum and liver was dependent on antibody mass. Normalized average values of the ratio of residence times between lesion and liver for 10, 25, 50 and 100mg of antibody were 1.0, 1.9, 3.2 and 4.0 respectively.
Dosimetric projections for radioimmunotherapy with 90Y-labeled J591 suggested similar absorbed doses to lesions, for treatment at the maximally tolerated activity (MTA), irrespective of antibody mass. However absorbed doses to liver at MTA would be antibody mass-dependent with estimates of 20, 10, 7 and 5 Gy for 10, 25, 50 and 100mg of J591respectively.
The proportion of the amount of antibody increased in lesions and decreased in the liver with increasing mass of administered antibody up to a dose of 50 mg. Proportional hepatic uptake continued to decrease with increasing antibody mass up to 100 mg. The optimal antibody mass for radioimmunotherapy would therefore appear to be greater than or equal to 50mg.
PMCID: PMC2766795  PMID: 18552139
J591 antibody; prostate cancer; radioimmunotherapy; dosimetry

Results 1-13 (13)