Radiolabeling of PSMA-617 with 89Zr: A Novel Use of DMSO for Radiochemical Yield Enhancement and Preliminary Small-Animal PET Results

Introduction: Prostate-specific membrane antigen (PSMA)-targeted ligands, including PSMA-617, have been developed for theranostics of prostate cancer. 68Ga-PSMA-617 is the de facto standard of PSMA Positron Emission Tomography (PET) for imaging in prostate cancer patients prior to radioligand therapy (RLT) with 177Lu-PSMA-617. The dose-limiting toxicity for PSMA-RLT is damage to the kidney. PET scans using 68Ga-PSMA-617 have to be performed within a few hours of injection due to its short half-life (68 min). However, the presence of radioactivity in urine at the PET imaging timepoint hampers the dose optimization of 177Lu (half-life 6.6 d)-labeled PSMA-617. Thus, the long-lived positron emitter 89Zr (half-life 3.3 d) is suited for optimizing the doses of 177Lu-PSMA-617 because PET scans can be performed after excretion of radioactive urine. Although 89Zr has great potential for PET imaging, its inadequate incorporation into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), limits its applications. Here, we report the radiolabeling of PSMA-617 with 89Zr and preliminary PET imaging studies using 89Zr-PSMA-617. Methods: DMSO and HEPES buffer were used to label PSMA-617 with 89Zr. The dissociation constant (Kd) of 89Zr-PSMA-617 was determined using a cell-binding assay. Delayed-PET scans using 89Zr-PSMA-617 were performed at 24 h (N = 5). Results: 89Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The Kd value was 6.8 nM. In PET imaging, standardized uptake value (SUV) was highest in LNCaP tumors (SUVmax = 0.98 ± 0.32), whereas it was low in kidney (SUVmax = 0.18 ± 0.7). Conclusion: The preparation of 89Zr-PSMA-617 was achieved by using the DMSO and HEPES buffer. 89Zr-PSMA-617 visualize the PSMA positive LNCaP tumors without accumulation in bladder. Advances in knowledge and implications for patient care: The use of 89Zr-PSMA-617 to predict the radiation doses in normal tissues lead to safe and effective RLT with 177Lu-PSMA-617.

The use of HEPES-buffer in the production of gallium-68 radiopharmaceuticals – time to reconsider strict pharmacopoeial limits?

HEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration.This short communication summarizes data from the literature on the toxicity of HEPES in dogs after intravenous infusion and the subsequent use in humans. We also highlight the use of HEPES in an FDA labelled intravenous drug formulation. Regulatory institutions may consider this data to review current strict limits.

POTENSI KOMBINASI AMIDO-BRIDGED NUCLEIC ACID MODIFIED ANTISENSE OLIGONUCLEOTIDES DENGAN POLYAMIDOAMINE DENDRIMER GENERASI 4 TERTARGET Α-SYNUCLEIN SEBAGAI TERAPI PARKINSON

Parkinson adalah penyakit neurodegeneratif yang meningkat lebih cepat daripada gangguan neurologis lainnya. Saat ini pengobatan Parkinson menggunakan dopamine agonist dan levodopa, namun pengobatan ini memiliki efek samping seperti menurunkan nafsu makan dan tidak berfokus pada pencegahan kematian neuron. Salah satu protein yang berperan dalam patogenesis dari Parkinson adalah protein α-synuclein, di mana agregasi dan misfolding dari protein ini bersifat toksik pada neuron sehingga mendukung progresi Parkinson. Antisense oligonucleotide (ASO) yang dikombinasikan dengan amido-bridge nucleic acid (AmNA) diketahui memiliki efek untuk menekan ekspresi mRNA α-synuclein namun hanya sebagian kecil dosis yang terdistribusi ke jaringan target sehingga diperlukan karier yang stabil. Polyamidoamine (PAMAM) Dendrimer menjadi pilihan dengan kemampuan menembus Blood Brain Barrier dan menarget organ secara spesifik. Secara khusus, PAMAM Dendrimer Generasi 4 (PAMAM G4) dapat menghambat agregasi protein α-synuclein. Oleh karena itu, mengombinasikan potensi yang dimiliki oleh AmNA-ASO dengan PAMAM Dendrimer Generasi 4 menggunakan larutan HEPES buffer diharapkan mampu menjadi terapi Parkinson yang menjanjikan.

Ratiometric sensing of Zn2+ with a new benzothiazole-based fluorescent sensor and living cell imaging

A new fluorescent probe, 3-(Benzo[d]thiazol-2-yl)-5-bromosalicylaldehyde-4N-phenyl thiosemicarbazone (BTT) for ratiometric sensing of Zn2+ ions in methanol / HEPES buffer solution (3 : 2, pH = 7.4) is reported in this paper....

A Highly Emissive Zn(II)-pyridyl-benzimidazolyl-phenolato based Chemosensor: Detection of H2PO4‒ via “Use” and “Throw” Device Fabrication

2-Ethoxy-6-[1-(phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-phenol (HL) selectively serves as sensitive ‘turn on’ Zn2+ sensor in 9:1 (v/v) DMSO/H2O (HEPES Buffer, pH=7.4) medium in presence of sixteen other cations at the limit of detection (LOD)...

Zinc and Nickel signature for abiogenic and biogenic magnetite: implications for the origin of magnetite in banded iron formations

<p>There are longstanding and ongoing controversies about the abiogenic or biogenic origin of magnetite in banded iron formations (BIFs). The trace element composition of magnetite was proposed as a promising tracer for distinguishing biogenic from abiogenic magnetite, which, however, remains to be explored quantitatively. Here, we compared the partitioning of trace elements Zinc (Zn) and Nickel (Ni) in both abiogenic and biogenic magnetite produced either by an abiotic reaction of ferrihydrite with by Fe<sup>2+</sup><sub>aq</sub> or by Fe(III)-reducing bacteria <em>Shewanella oneidensis</em> MR-1. We compared the transformation of three different ferrihydrite (Fh) starting materials: 1) Control Fh without added trace elements, 2) ferrihydrite with co-precipitated Zn (ZnFh) and 3) ferrihydrite with co-precipitated Ni (NiFh) – both in either NaHCO<sub>3</sub> or HEPES buffer. We monitored Fe concentration and speciation in both aqueous and solid phases over time using the spectrophotometric ferrozine assay, analyzed Fh transformation products by Mössbauer spectroscopy as well as X-ray diffraction and quantified Zn and Ni in solution and in the minerals by iCAP-Qc quadrupole mass spectrometer after acidic dissolution of the minerals. In summary our results revealed that both Zn and Ni are much more depleted in abiogenic magnetite than those in biogenic magnetite, independent of whether magnetite was precipitated in NaHCO<sub>3</sub> or HEPES buffer. Although further analyses are needed, this suggests that the trace element distribution could be a chemical signature to distinguish biogenic from abiogenic magnetite in BIFs.</p>

A highly selective colorimetric fluorescence probe for Cu2+ in aqueous media: the synthesis, DFT investigation and its application in living cells

A novel highly selective colorimetric fluorescence probe, POPH, has been successfully synthesized and it shows remarkable selective and sensitive response to Cu2+ in aqueous media (HEPES buffer, pH = 7.4).