PURPOSE Studies herein explore paclitaxel enhancement of the therapeutic efficacy of alpha-particle-targeted radiation therapy. EXPERIMENTAL DESIGN Athymic mice bearing 3 day i.p. LS-174T xenografts were treated with 300 or 600 microg paclitaxel at 24 h before, concurrently, or 24 h after [213Bi] or [212Pb]trastuzumab. RESULTS Paclitaxel (300 or 600 microg) followed 24 h later with [213Bi]t...

BACKGROUND Up to now, prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy mainly focused on β-emitting radionuclides. Herein, two new 213Bi-labeled agents for PSMA-targeted α therapy of prostate cancer (PCa) are reported. METHODS The biodistribution of 213Bi-labeled small-molecule inhibitor PSMA I&T and nanobody JVZ-008 was evaluated in mice bearing PSMA-positive LNCaP xen...

Lintuzumab, a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest activity against acute myeloid leukemia (AML). To increase the antibody’s potency yet avoid nonspecific cytotoxicity seen with -emitting isotopes, lintuzumab was conjugated to the -emitters bismuth-213 (213Bi) and actinium-225 (225Ac). The 46-minute half-life of 213Bi limits its widespread use. Therefore...

Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of infection. In this study, we investigated the microbicidal properties of an alpha particle-emitting 213Bi-labeled monoclonal antibody (MAb), EA2-1 (213Bi-EA2-1), that binds to the immunodominant antigen on Bacillus anthracis spore...

BACKGROUND The aim of this study was to compare the therapeutic efficacy of two different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of 213Bi-MX35, 3 MBq/mL (n = 20), o...

BACKGROUND Targeted alpha therapy (TAT) offers advantages over current β-emitting conjugates for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. PRRT with 177Lu-DOTATATE or 90Y-DOTATOC has shown dose-limiting nephrotoxicity due to radiopeptide retention in the proximal tubules. Pharmacological protection can reduce renal uptake of radiopeptides, e.g., positively charged a...

BACKGROUND Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-...

Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides. The daughters, especially bismuth-213 (213Bi), tend to accumulate in the kidn...

Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)–streptavidin (SA) conjugate and DOTA-biotin labeled with -emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. -emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to -emit...

Despite the large interest in nuclear/optical multimodality imaging, the effect of radiation on the fluorescence of fluorophores remains largely unexplored. Herein, we report on the radiobleaching of cyanine fluorophores and describe conditions to provide robust radioprotection under practical (pre)clinical settings. We determined the radiosensitivity of several cyanine fluorescent compounds, i...