Heike E. Daldrup-Link, MD, Ph.D.

A combination of anti-cancer antibodies produced a powerfully synergistic response in two hard-to-treat pediatric cancers, according to a new study, in mice, led by researchers at the Stanford University School of Medicine.

The results, which published online Jan. 13 in Nature Medicine, provide hope for better treatments of neuroblastoma, a cancer affecting young children that develops from nerve cells, and osteosarcoma, a bone cancer most often seen in teens and young adults. One-third to one-half of patients with these cancers either never respond to treatments such as chemotherapy, radiation and surgery or respond but then suffer a relapse. Most of these patients die of the disease… Continue reading.

Using whole body diffusion-weighted magnetic resonance imaging (DW MRI) to evaluate the efficacy on cancer treatment in children can potentially provide a more than three-quarters cut in radiation exposure, according to new research.

A study, funded by the National Institutes of Health (NIH), published today in Radiology shows that DW MRI can track tumor response to therapy as effectively as techniques using CT scans, but without radiation.

The researchers had financial support from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

To determine whether this technique was feasible and effective, investigators, led by Heike E. Daldrup-Link, M.D., Ph.D., of Stanford University, compared DW MRI to an established technique – fluorine 18 fluorodeoxyglucose positron emission tomography (FDG PET). DW MRI measures tumor density by tracking water molecule movement in tissue, and FDG PET is frequently used with CT to measure tumor metabolism after radioactive glucose injection… Continue reading.

Abstract

The long-term survival of osteosarcoma patients with metastatic or recurrent disease remains dismal, and new therapeutic options are urgently needed. The purpose of our study was to compare the efficacy of CD47 mAb plus doxorubicin combination therapy in mouse models of osteosarcoma with CD47 mAb and doxorubicin monotherapy. Forty-eight NOD scid gamma (NSG) mice with intratibial MNNG/HOS tumors received CD47 mAb, doxorubicin, combination therapy, or control IgG treatment. Twenty-four mice (n = 6 per group) underwent pre- and post-treatment magnetic resonance imaging (MRI) scans with the macrophage marker ferumoxytol, bioluminescence imaging, and histological analysis. Tumor ferumoxytol enhancement, tumor flux, and tumor-associated macrophages (TAM) density were compared between different groups using a one-way ANOVA. Twenty-four additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log-rank (Mantel-Cox) test. Intratibial osteosarcomas demonstrated significantly stronger ferumoxytol enhancement and significantly increased TAM quantities after CD47 mAb plus doxorubicin combination therapy compared to CD47 mAb (P = 0.02) and doxorubicin monotherapy (P = 0.001). Tumor-bearing mice treated with CD47 mAb plus doxorubicin combination therapy demonstrated significantly reduced tumor size and prolonged survival compared to control groups that received CD47 mAb (P = 0.03), doxorubicin monotherapy (P = 0.01), and control IgG (P = 0.001). In conclusion, CD47 mAb plus doxorubicin therapy demonstrates an additive therapeutic effect in mouse models of osteosarcomas, which can be monitored with an immediately clinically applicable MRI technique… Read the full text.

Abstract

Background

Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair.

Purpose

To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation.

Results

Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks.

Conclusion

Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model… Read the full text.

WASHINGTON, D.C.—The American Institute for Medical and Biological Engineering (AIMBE) has announced the induction of Heike E. Daldrup-Link, MD, Ph.D., Professor, Department of Radiology; Professor by courtesy, Department of Pediatrics; Director, Pediatric Molecular Imaging; Co-Director, Cancer Imaging & Early Detection; Associate Chair for Diversity, Department of Radiology, Stanford University School of Medicine, to its College of Fellows. Dr. Daldrup-Link was nominated, reviewed, and elected by peers and members of the College of Fellows for pioneering efforts driving development and clinical translation of nanoparticle MRI for cancer imaging and stem cell imaging.