Imaging Melphalan Therapy Response in Preclinical Extramedullary Myeloma with 18F-FDOPA and 18F-FDG PET

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Hathi D, DeLassus E, Achilefu S, McConathy J, Shokeen M. (2018)
DOI: 10.2967/jnumed.118.208744 download PDF from J Nucl Med

Abstract

Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B-cells that has resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small molecule DNA alkylating agent, are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 18F-FDOPA, a clinically available positron emission tomography (PET) radiotracer with specificity to the L-type amino acid transporter-1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM.

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Nanotherapeutics for Multiple Myeloma

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Alexander Zheleznyak, Monica Shokeen, Samuel Achilefu

Abstract

Multiple myeloma (MM) is an age‐related hematological malignancy with an estimated 30,000 new cases and 13,000 deaths per year. A disease of antibody‐secreting malignant plasma B‐cells that grow primarily in the bone marrow (BM), MM causes debilitating fractures, anemia, renal failure, and hypercalcemia. In addition to the abnormal genetic profile of MM cells, the permissive BM microenvironment (BMM) supports MM pathogenesis. Read More

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging

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Wu L, Wen X, Wang X, Wang C, Sun X, Wang K, Zhang H, Williams T, Stacy AJ, Chen J, Schmieder AH, Lanza GM, Shen B. (2018)

Abstract

Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Read More

Bone‐Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases

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Ross MH, Esser AK, Fox GC, Schmieder AH, Yang X, Hu G, Pan D, Su X, Xu Y, Novack DV, Walsh T, Colditz GA, Lukaszewicz GH, Cordell E, Novack J, Fitzpatrick JAJ, Waning DL, Mohammad KS, Guise TA, Lanza GM, Weilbaecher KN. (2017)
PMCID: PMC5841166 DOI: 10.1158/0008-5472.CAN-17-1225
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Abstract

Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. Read More

An unmet clinical need: The history of thrombus imaging

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Lanza GM, Cui G, Schmieder AH, Zhang H, Allen JS, Scott MJ, Williams T, Yang X. (2017)
https://link.springer.com/article/10.1007%2Fs12350-017-0942-8
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Abstract

Robust thrombus imaging is an unresolved clinical unmet need dating back to the mid 1970s. While early molecular imaging approaches began with nuclear SPECT imaging, contrast agents for virtually all biomedical imaging modalities have been demonstrated in vivo with unique strengths and common weaknesses. Two primary molecular imaging targets have been pursued for thrombus imaging: platelets and fibrin. Some common issues noted over 40 years ago persist today. Acute thrombus is readily imaged with all probes and modalities, but aged thrombus remains a challenge. Similarly, anti-coagulation continues to interfere with and often negate thrombus imaging efficacy, but heparin is clinically required in patients suspected of pulmonary embolism, deep venous thrombosis or coronary ruptured plaque prior to confirmatory diagnostic studies have been executed and interpreted. These fundamental issues can be overcome, but an innovative departure from the prior approaches will be needed.