Joseph J. Grudzinski
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View article: Radionuclide-Dependent Stimulation of Antitumor Immunity in GD2-Targeted Radiopharmaceutical Therapy Combined with Immune Checkpoint Inhibitors
Radionuclide-Dependent Stimulation of Antitumor Immunity in GD2-Targeted Radiopharmaceutical Therapy Combined with Immune Checkpoint Inhibitors Open
Radiopharmaceutical therapy (RPT) offers tumor-selective radiation delivery and represents a promising platform for combination with immune checkpoint inhibitors (ICIs). While prior studies suggest that RPT can stimulate antitumor immunity…
View article: Figure S5 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S5 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Longitudinal in vivo gene expression following 12 Gy EBRT (MOC2).
View article: Figure S9 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S9 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Tumor Ifnb1 expression following 225Ac-NM600+ICI is not affected by loss of STING expression in tumor or host.
View article: Figure S2 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S2 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Earlier induction of type I IFN response/immunologic response to radiation following 58mCo and 119Sb.
View article: Figure S6 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S6 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
90Y-, 177Lu, 225Ac-NM600 modulate tumor immune cell composition in the tumor microenvironment.
View article: Figure S8 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S8 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Individual tumor growth curves from Figure 6F.
View article: Data from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Data from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Radiopharmaceutical therapies (RPT) activate an IFN1 response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90Y, 177Lu, and 225Ac in vitro as unbound …
View article: Figure S4 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S4 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Representative images of γH2AX foci over time in (A) MOC2 (12 Gy) and (B) B78 (4 Gy) cells following EBRT, 90Y, 177Lu, and 225Ac.
View article: Figure S7 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S7 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
B78 WT vs. STING KO cell line in vitro Ifnb1 and Ddx58 gene expression upregulation following 225Ac or EBRT.
View article: Figure S1 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S1 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Specific activity maintained in radionuclide-containing cell culture media throughout media exchanges.
View article: Supplementary Tables from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Supplementary Tables from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Tables S1-S13
View article: Figure S3 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy
Figure S3 from The Effects of Clinically Relevant Radionuclides on the Activation of an IFN1 Response Correlate with Radionuclide Half-life and Linear Energy Transfer and Influence Radiopharmaceutical Antitumor Efficacy Open
Longitudinal Ifnb1, Mx1, Ddx58, Fas, Pdl1, and Mhc1 expression following (A) 12 Gy EBRT (MOC2) or (B) 4 Gy EBRT (B78) in vitro.
View article: Immunomodulatory effects of alpha vs beta radiopharmaceutical therapy in murine prostate cancer
Immunomodulatory effects of alpha vs beta radiopharmaceutical therapy in murine prostate cancer Open
Background Radiation therapy can modulate the tumor microenvironment (TME), influencing antitumor immune responses. This study compared the immunomodulatory effects of alpha-emitting ( 225 Ac) and beta-emitting ( 177 Lu) radiopharmaceutica…
View article: Priming versus propagating: distinct immune effects of an alpha- versus beta-particle emitting radiopharmaceutical when combined with immune checkpoint inhibition
Priming versus propagating: distinct immune effects of an alpha- versus beta-particle emitting radiopharmaceutical when combined with immune checkpoint inhibition Open
Radiopharmaceutical therapy (RPT) enhances tumor response to immune checkpoint inhibitors (ICI) in preclinical models, but the effects of different radioisotopes have not been thoroughly compared. To evaluate mechanisms of response to RPT+…
View article: Effects of clinically relevant radionuclides on the activation of a type I interferon response by radiopharmaceuticals in syngeneic murine tumor models
Effects of clinically relevant radionuclides on the activation of a type I interferon response by radiopharmaceuticals in syngeneic murine tumor models Open
Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90 Y, 177 Lu, and 225 A…
View article: Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody
Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody Open
Background: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. H…
View article: Creation of waterproof, TLD probes for dose measurements to validate image-based radiopharmaceutical therapy dosimetry workflow
Creation of waterproof, TLD probes for dose measurements to validate image-based radiopharmaceutical therapy dosimetry workflow Open
Voxel-level dosimetry based on nuclear medicine images offers patient-specific personalization of radiopharmaceutical therapy (RPT) treatments. Clinical evidence is emerging demonstrating improvements in treatment precision in patients whe…
View article: Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry
Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry Open
Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primar…
View article: Radiation to all macroscopic sites of tumor permits greater systemic antitumor response to in situ vaccination
Radiation to all macroscopic sites of tumor permits greater systemic antitumor response to in situ vaccination Open
Background The antitumor effects of external beam radiation therapy (EBRT) are mediated, in part, by an immune response. We have reported that a single fraction of 12 Gy EBRT combined with intratumoral anti-GD2 hu14.18-IL2 immunocytokine (…
View article: Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment
Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment Open
Targeted radionuclide therapy (TRT) and immunotherapy are rapidly growing classes of cancer treatments. Basic, translational, and clinical research are now investigating therapeutic combinations of these agents. In comparison to external b…
View article: 870 High-dose radiation is required for effective combination with tumor-specific vaccination in a prostate cancer model
870 High-dose radiation is required for effective combination with tumor-specific vaccination in a prostate cancer model Open
Background The approval of Sipuleucel-T demonstrates the value of antigen-specific vaccination approaches for prostate cancer. We have studied a DNA vaccine specific for the ligand-binding domain of the androgen receptor (pTVG-AR) as a mor…
View article: Profound immunomodulatory effects of <sup>225</sup>Ac-NM600 drive enhanced anti-tumor response in prostate cancer
Profound immunomodulatory effects of <sup>225</sup>Ac-NM600 drive enhanced anti-tumor response in prostate cancer Open
An immunosuppressive tumor microenvironment has hampered the efficacy of immunotherapy in prostate cancer. However, radiation-induced immunological effects can partly mediate anti-tumor effects by promoting a pro-inflammatory environment p…
View article: Antitumor efficacy of <sup>90</sup>Y-NM600 targeted radionuclide therapy and PD-1 blockade is limited by regulatory T cells in murine prostate tumors
Antitumor efficacy of <sup>90</sup>Y-NM600 targeted radionuclide therapy and PD-1 blockade is limited by regulatory T cells in murine prostate tumors Open
Background Systemic radiation treatments that preferentially irradiate cancer cells over normal tissue, known as targeted radionuclide therapy (TRT), have shown significant potential for treating metastatic prostate cancer. Preclinical stu…
View article: Validation of Monte Carlo <sup>131</sup>I radiopharmaceutical dosimetry workflow using a 3D‐printed anthropomorphic head and neck phantom
Validation of Monte Carlo <sup>131</sup>I radiopharmaceutical dosimetry workflow using a 3D‐printed anthropomorphic head and neck phantom Open
Purpose Approximately 50% of head and neck cancer (HNC) patients will experience loco‐regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may b…
View article: Clinical Imaging and Dosimetry of a Pan-Cancer Targeting Alkylphosphocholine Analog, [124I]I-NM404
Clinical Imaging and Dosimetry of a Pan-Cancer Targeting Alkylphosphocholine Analog, [124I]I-NM404 Open
The purpose of this study was to assess organ dosimetry and clinical use of [124I]I-NM404, a radiotheranostic alkylphosphocholine (APC) analog, for accurate detection and characterization of a wide variety of solid primary and metastatic m…
View article: Partial volume correction improves theranostic 124I/131I-CLR1404 tumor dosimetry in xenograft models of head and neck cancer
Partial volume correction improves theranostic 124I/131I-CLR1404 tumor dosimetry in xenograft models of head and neck cancer Open
Combination radiopharmaceutical and external beam radiotherapy offers the potential to diminish locoregional toxicity that remains dose-limiting in the conventional treatment paradigm for recurrent head and neck cancer (HNC). In this study…
View article: Validation of Monte Carlo Iodine-131 radiopharmaceutical dosimetry workflow using a 3D printed anthropomorphic head and neck phantom
Validation of Monte Carlo Iodine-131 radiopharmaceutical dosimetry workflow using a 3D printed anthropomorphic head and neck phantom Open
Purpose: In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom and its characterization for the validation of a Monte Carlo, SPECT image based, Iodine-131 RPT dosimetry workflow. Methods: 3D …
View article: 594 Combination of antigen-specific vaccination and targeted radionuclide therapy improves anti-tumor efficacy in a murine prostate model
594 Combination of antigen-specific vaccination and targeted radionuclide therapy improves anti-tumor efficacy in a murine prostate model Open
Background While checkpoint blockade has been unsuccessful in prostate cancer trials, the approval of Sipuleucel-T demonstrates the value of antigen-specific vaccination approaches for this disease. We have studied a DNA vaccine specific f…