A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer.

Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration-resistant prostate cancer (mCRPC). Although prostate-specific membrane antigen is the only cell-surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor-directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate-specific target with little to no expression in nonprostate tissues.

First-in-Human Evaluation of Site-Specifically Labeled Zr-Pertuzumab in Patients with HER2-Positive Breast Cancer.

Radioimmunoconjugates targeting human epidermal growth factor receptor 2 (HER2) have shown potential to noninvasively visualize HER2-positive tumors. However, the stochastic approach that has been traditionally used to radiolabel these antibodies yields poorly defined and heterogeneous products with suboptimal in vivo performance. Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry of Zr-site-specific (ss)-pertuzumab PET, a site-specifically labeled radioimmunoconjugate designed to circumvent the limitations of random stochastic lysine labeling.

A Phase 1, Open-label, Dose-Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095 for the Treatment of Metastatic Castration-Resistant Prostate Cancer.

Purpose: 131I-MIP-1095 is a targeted radiotherapeutic that contains 131I, a β-particle emitter, and MIP-1095, a urea-based ligand for prostate-specific membrane antigen. We report the first phase 1, dose-escalation study of 131I-MIP-1095 in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: This study enrolled men with mCRPC refractory to second-generation antiandrogen(s) and taxane chemotherapy.

Lesion Dosimetry for [Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [Lu]Lu-PSMA-617 (7.

Noninvasive Assessment of Human Epidermal Growth Factor Receptor 2 (HER2) in Esophagogastric Cancer Using Zr-Trastuzumab PET: A Pilot Study.

Variations in human epidermal growth factor receptor 2 (HER2) expression between the primary tumor and metastases may contribute to drug resistance in HER2-positive (HER2+) metastatic esophagogastric cancer (mEGC). Zr-trastuzumab PET (HER2 PET) holds promise for noninvasive assessment of variations in HER2 expression and target engagement. The aim of this study was to describe HER2 PET findings in patients with mEGC.

Improved image reconstruction of Zr-immunoPET studies using a Bayesian penalized likelihood reconstruction algorithm.

Purpose: The aim of this study was to evaluate the use of a Bayesian penalized likelihood reconstruction algorithm (Q.Clear) for Zr-immunoPET image reconstruction and its potential to improve image quality and reduce the administered activity of Zr-immunoPET tracers.

Methods: Eight Zr-immunoPET whole-body PET/CT scans from three Zr-immunoPET clinical trials were selected for analysis.

Theranostics: The Role of Quantitative Nuclear Medicine Imaging.

Theranostics is a precision medicine discipline that integrates diagnostic nuclear medicine imaging with radionuclide therapy in a manner that provides both a tumor phenotype and personalized therapy to patients with cancer using radiopharmaceuticals aimed at the same target-specific biological pathway or receptor. The aim of quantitative nuclear medicine imaging is to plan the alpha or beta-emitting therapy based on an accurate 3-dimensional representation of the in-vivo distribution of radioactivity concentration within the tumor and normal organs/tissues in a noninvasive manner. In general, imaging may be either based on positron emission tomography (PET) or single photon emission computed tomography (SPECT) invariably in combination with X-ray CT (PET/CT; SPECT/CT) or, to a much lesser extent, MRI.

Comparison of Ga-DOTA-JR11 PET/CT with dosimetric Lu-satoreotide tetraxetan (Lu-DOTA-JR11) SPECT/CT in patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy.

Purpose: Paired imaging/therapy with radiolabeled somatostatin receptor (SSTR) antagonists is a novel approach in neuroendocrine tumors (NETs). The aim of this study was to compare tumor uptake of Ga-DOTA-JR11 and Lu-satoreotide tetraxetan (Lu-DOTA-JR11) in patients with NETs.

Methods: As part of a prospective clinical trial, 20 patients with metastatic NETs underwent Ga-DOTA-JR11 PET/CT and serial imaging with Lu-satoreotide tetraxetan.

CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human Imaging.

Background Current measurements of multiple myeloma disease burden are suboptimal. Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on nearly all myeloma cells. Purpose To demonstrate preclinical and first-in-human application of an antibody composed of the native daratumumab labeled with the positron-emitting radionuclide zirconium 89 (Zr) through the chelator deferoxamine (DFO), or Zr-DFO-daratumumab, for immunologic PET imaging of multiple myeloma.

Safety and Feasibility of PARP1/2 Imaging with F-PARPi in Patients with Head and Neck Cancer.

Purpose: We performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with F-PARPi in patients with head and neck cancer.

Patients And Methods: Eleven patients with newly diagnosed or recurrent oral and oropharyngeal cancer were injected with F-PARPi (331 ± 42 MBq), and dynamic PET/CT imaging was performed between 0 and 25 minutes postinjection.

First-in-Humans Imaging with Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting.

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

Purpose: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer.

Patients And Methods: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163.

Phase I Trial of Well-Differentiated Neuroendocrine Tumors (NETs) with Radiolabeled Somatostatin Antagonist Lu-Satoreotide Tetraxetan.

Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist Lu-satoreotide tetraxetan.

Patients And Methods: Twenty patients with advanced SSTR2-positive NETs were treated with Lu-satoreotide tetraxetan.

Zr-Immuno-PET: Toward a Noninvasive Clinical Tool to Measure Target Engagement of Therapeutic Antibodies In Vivo.

Zr-immuno-PET is a promising noninvasive clinical tool that measures target engagement of monoclonal antibodies (mAbs) to predict toxicity in normal tissues and efficacy in tumors. Quantification of Zr-immuno-PET will need to move beyond SUVs, since total uptake may contain a significant non-target-specific contribution. Nonspecific uptake is reversible (e.

Pharmacokinetics and Biodistribution of a [Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients.

A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry.

Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using Zr-DFO-MSTP2109A Anti-STEAP1 Antibody.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified target in prostate cancer. We evaluated the ability of PET/CT with Zr-DFO-MSTP2109A, an antibody that recognizes STEAP1, to detect lesions in patients with metastatic castration-resistant prostate cancer (mCRPC). Nineteen mCRPC patients were prospectively imaged using approximately 185 MBq/10 mg of Zr-DFO-MSTP2109A.

Biodistribution and radiation dose estimates for Ga-DOTA-JR11 in patients with metastatic neuroendocrine tumors.

Purpose: Somatostatin receptor antagonists have shown promise for imaging neuroendocrine tumors (NETs) in preclinical studies, but clinical data is still very limited. In this study, we assess the feasibility of using the novel somatostatin antagonist Ga-DOTA-JR11 for PET imaging of NETs.

Methods: Twenty patients with advanced NETs underwent whole-body PET/CT imaging 60 min after injection of 169 MBq (median) Ga-DOTA-JR11 as part of a prospective study.

I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma.

Background: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer.

In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of Zr-pertuzumab PET/CT for human epidermal growth factor receptor 2 (HER2)-targeted imaging in patients with HER2-positive breast cancer. Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an institutional review board-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with Zr.

Pharmacokinetics, Biodistribution, and Radiation Dosimetry for Zr-Trastuzumab in Patients with Esophagogastric Cancer.

Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete, and most patients develop progression. To our knowledge, this is the first report evaluating Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry Zr-trastuzumab.

Monitoring early response to chemoradiotherapy with F-FMISO dynamic PET in head and neck cancer.

Purpose: There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC.

Multiparametric Imaging of Tumor Hypoxia and Perfusion with F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer.

Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with F-fluoromisonidazole (F-FMISO) dynamic PET (dPET) in head and neck cancer. One hundred twenty head and neck cancer patients underwent 0- to 30-min F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection.

Bombesin Antagonist-Based Radiotherapy of Prostate Cancer Combined with WST-11 Vascular Targeted Photodynamic Therapy.

DOTA-AR, a bombesin-antagonist peptide, has potential clinical application for targeted imaging and therapy in gastrin-releasing peptide receptor (GRPr)-positive malignancies when conjugated with a radioisotope such as Y. This therapeutic potential is limited by the fast washout of the conjugates from the target tumors. WST-11 (Weizmann STeba-11 drug; a negatively charged water-soluble palladium-bacteriochlorophyll derivative, Tookad Soluble) vascular targeted photodynamic therapy (VTP) is a local ablation approach recently approved for use in early-stage prostate cancer.