Next-Generation Cancer Magnetic Resonance Imaging With Tumor-Targeted Alkylphosphocholine Metal Analogs.

Objectives: In an effort to exploit the elevated need for phospholipids displayed by cancer cells relative to normal cells, we have developed tumor-targeted alkylphosphocholines (APCs) as broad-spectrum cancer imaging and therapy agents. Radioactive APC analogs have exhibited selective uptake and prolonged tumor retention in over 50 cancer types in preclinical models, as well as over 15 cancer types in over a dozen clinical trials. To push the structural limits of this platform, we recently added a chelating moiety capable of binding gadolinium and many other metals for cancer-targeted magnetic resonance imaging (MRI), positron emission tomography imaging, and targeted radionuclide therapy.

Docking of Alkylphosphocholine Analogs to Human Serum Albumin Predicts Partitioning and Pharmacokinetics.

Alkylphosphocholine (APC) analogs are a novel class of broad-spectrum tumor-targeting agents that can be used for both diagnosis and treatment of cancer. The potential for clinical translation for APC analogs will strongly depend on their pharmacokinetic (PK) profiles. The aim of this work was to understand how the chemical structures of various APC analogs impact binding and PK.

Beyond the margins: real-time detection of cancer using targeted fluorophores.

Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging.

Diapeutic cancer-targeting alkylphosphocholine analogs may advance management of brain malignancies.

The following is a special report on alkylphosphocholine analogs as targeted imaging and therapy agents for cancer, and their potential role in diagnosis and treatment in glioblastoma and brain metastases. These novel cancer-targeting agents display impressive tumor avidity with low background in the normal brain, and multimodal diagnostic imaging and therapy capabilities. The use of these agents may significantly improve diagnosis, treatment and post-treatment follow-up in patients with brain malignancies.

Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood-Brain Barrier Model.

Cancer-targeting alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure-activity studies. While they strongly label human brain cancers associated with disrupted blood-brain barriers (BBB), APC permeability across intact BBB remains unknown.

Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection.

Background: 5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery.

Objective: To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA.

Monte Carlo comparison of superficial dose between flattening filter free and flattened beams.

This study investigates the superficial dose from FFF beams in comparison with the conventional flattened ones using a Monte Carlo (MC) method. Published phase-space files which incorporated real geometry of a TrueBeam accelerator were used for the dose calculation in phantom and clinical cases. The photon fluence on the central axis is 3 times that of a flattened beam for a 6 MV FFF beam and 5 times for a 10 MV beam.

Is wax equivalent to tissue in electron conformal therapy planning? A Monte Carlo study of material approximation introduced dose difference.

With CT-based Monte Carlo (MC) dose calculations, material composition is often assigned based on the standard Hounsfield unit ranges. This is known as the density threshold method. In bolus electron conformal therapy (BolusECT), the bolus material, machineable wax, would be assigned as soft tissue and the electron density is assumed equivalent to soft tissue based on its Hounsfield unit.

Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: a dosimetric comparison with 3D technique.

Purpose: Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion.

Dosimetric analysis of modulated and hybrid arcs in stereotactic radiosurgery.

Purpose: Forward-planned conformal arcs (termed dynamic arcs in the BrainLab iPlan system) have been routinely used in cranial stereotactic radiosurgery (SRS) for many yeras. This study compares dosimetric parameters of the newer, inversely-planned volumetric modulated arc therapy (VMAT) and VMAT-conformal hybrid plans with conformal arc plans. In the hybrid plans, various numbers of conformal arcs in a conformal plan are replaced with VMAT arcs.