Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

<div><p>Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to <i>manganism</i>. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide ⁵²Mn (<i>t</i>_<i>1/2</i> = 5.6 d) by proton bombardment (<i>E</i>_<i>p</i><15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography. An aqueous solution of [⁵²Mn]MnCl₂ was nebulized into a closed chamber with openings through which mice inhaled the aerosol, and a separate cohort of mice received intravenous (IV) injections of [⁵²Mn]MnCl₂. <i>Ex vivo</i> biodistribution was performed at 1 h and 1 d post-injection/inhalation (p.i.). In both trials, we observed uptake in lungs and thyroid at 1 d p.i. Manganese is known to cross the blood-brain barrier, as confirmed in our studies following IV injection (0.86%ID/g, 1 d p.i.) and following inhalation of aerosol, (0.31%ID/g, 1 d p.i.). Uptake in salivary gland and pancreas were observed at 1 d p.i. (0.5 and 0.8%ID/g), but to a much greater degree from IV injection (6.8 and 10%ID/g). In a separate study, mice received IV injection of an imaging dose of [⁵²Mn]MnCl₂, followed by <i>in vivo</i> imaging by positron emission tomography (PET) and <i>ex vivo</i> biodistribution. The results from this study supported many of the results from the biodistribution-only studies. In this work, we have confirmed results in the literature and contributed new results for the biodistribution of inhaled radiomanganese for several organs. Our results could serve as supporting information for environmental and occupational regulations, for designing PET studies utilizing ⁵²Mn, and/or for predicting the biodistribution of manganese-based MR contrast agents.</p></div

Cyclotron production of high–specific activity 55Co and in vivo evaluation of the stability of 55Co metal-chelate-peptide complexes

This work describes the production of high–specific activity 55 Co and the evaluation of the stability of 55 Co-metal-chelate-peptide complexes in vivo. 55 Co was produced via the 58 Ni(p,α) 55 Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55 Co-DO3A and 55 Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55 CoCl 2 . Both 55 Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers’ uptake in the liver by sixfold at 24 hours with ˜ 1% ID/g and at 48 hours with ˜ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ˜ 0.7% ID/g and sevenfold at 48 hours with ˜ 0.35% ID/g. These results support the use of 55 Co as a promising new radiotracer for PET imaging of cancer and other diseases

Immuno-PET of epithelial ovarian cancer: Harnessing the potential of CA125 for non-invasive imaging

BACKGROUND: Epithelial ovarian cancer (EOC) is characterized by the overexpression of cancer antigen 125 (CA125), a mucinous glycoprotein that serves as a tumor biomarker. Early diagnosis of EOC is plagued by its asymptomatic nature of progression and the limitations of currently used immunoassay techniques that detect CA125 as a shed antigen in serum samples. Presently, there is no technique available for the in vivo evaluation of CA125 expression in malignant tissues. Moreover, there could be an unexplored pathophysiological time window for the detection of CA125 in EOC, during which it is expressed on tumor cells prior to being shed into the bloodstream. A method for the in vivo evaluation of CA125 expression on ovarian neoplasms earlier along disease progression and/or recurrence can potentially contribute to better disease management. To this end, the present work utilizes an anti-CA125 monoclonal antibody (MAb) and a single-chain variable fragment (scFv) labeled with the positron-emitting radionuclide (64)Cu for preclinical molecular imaging of CA125 expression in vivo. METHODS: Anti-CA125 MAb and scFv were prepared and functionally characterized for target binding prior to being tested as radiotracers in a preclinical setting. RESULTS: Immunoblotting, immunofluorescence, and flow cytometry revealed specific binding of CA125-targeting vectors to NIH:OVCAR-3 cells and no binding to antigen-negative SKOV3 cells. (64)Cu-labeled anti-CA125 MAb and scFv were obtained in specific activities of 296 and 122 MBq/mg, respectively. Both radioimmunoconjugate vectors demonstrated highly selective binding to NIH:OVCAR-3 cells and virtually no binding to SKOV3 cells. In vivo radiopharmacological evaluation using xenograft mouse models injected with (64)Cu-labeled anti-CA125 MAb provided a standardized uptake value (SUV) of 5.76 (29.70 %ID/g) in OVCAR3 tumors 24 h post-injection (p.i.) versus 1.80 (5.91 %ID/g) in SKOV3 tumors. (64)Cu-labeled anti-CA125 scFv provided an SUV of 0.64 (3.21 %ID/g) in OVCAR3 tumors 24 h p.i. versus 0.25 (1.49 %ID/g) in SKOV3 tumors. Results from small-animal PET imaging were confirmed by ex vivo autoradiography and immunohistochemistry. CONCLUSIONS: Radiolabeling of anti-CA125 MAb and scFv with (64)Cu did not compromise their immunoreactivity. Both radioimmunoconjugates presented specific tumor uptake and expected biological clearance profiles. This renders them as potential immuno-PET probes for targeted in vivo molecular imaging of CA125 in EOC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-014-0060-4) contains supplementary material, which is available to authorized users

Feasibility of isotope harvesting at a projectile fragmentation facility: ⁶⁷Cu

The work presented here describes a proof-of-principle experiment for the chemical extraction of (67)Cu from an aqueous beam stop at the National Superconducting Cyclotron Laboratory (NSCL). A 76 MeV/A (67)Cu beam was stopped in water, successfully isolated from the aqueous solution through a series of chemical separations involving a chelating disk and anion exchange chromatography, then bound to NOTA-conjugated Herceptin antibodies, and the bound activity was validated using instant thin-layer chromatography (ITLC). The chemical extraction efficiency was found to be 88 ± 3% and the radiochemical yield was ≥95%. These results show that extraction of radioisotopes from an aqueous projectile-fragment beam dump is a feasible method for obtaining radiochemically pure isotopes

Synthesis, complex stability and small animal PET imaging of a novel 64Cu-labelled cryptand molecule

The radiosynthesis and radiopharmacological evaluation including small animal PET imaging of a novel 64Cu-labelled cryptand molecule ([64Cu]CryptTM) possessing a tris-pyridyl/tris-amido set of donor atoms is described

Pulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors

Study describes the use of a non-cytotoxic dose of histone deacetylase (HDAC) inhibitors to induce pulmonary carcinoid somatostatin receptor subtype 2 (SSTR2) expression to diagnose pulmonary carcinoids