title: Evaluation of a PSMA-targeted BNF nanoparticle construct.
abstract: Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 ± 0.4 percentage injected dose per gram of tissue (%ID g(-1))], with tumor/blood and tumor/muscle ratios of 7.5 ± 2.4 and 11.6 ± 1.2 %ID g(-1), respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo.
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mpomper@jhmi.edu.
authors: Babak
authors: B
authors: Behnam Azad
authors: Sangeeta R
authors: SR
authors: Banerjee
authors: Mrudula
authors: M
authors: Pullambhatla
authors: Silvia
authors: S
authors: Lacerda
authors: Catherine A
authors: CA
authors: Foss
authors: Yuchuan
authors: Y
authors: Wang
authors: Robert
authors: R
authors: Ivkov
authors: Martin G
authors: MG
authors: Pomper
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D005290:Ferric Compounds; C001215:ferrite; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II