Role of FDG PET/CT in Management of Patients with Prostate Cancer.

Prostate cancer is the second most common cancer in men worldwide. [F]FDG PET/CT imaging, a well-known and effective technique for detecting malignancies, has not been considered a useful tool for prostate cancer imaging by many because of its perceived low [F]FDG uptake. Incidentally detected focal [F]FDG uptake in the prostate is not uncommon, and typically benign.

Safety of Lutetium-177 prostate-specific membrane antigen-617 (PSMA-617) radioligand therapy in the setting of severe renal impairment: a case report and literature review.

Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [Lu]Lu-PSMA-617 therapy. Multidisciplinary input, individualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits.

Toxicity and Tolerability of Lu-DOTA-TATE PRRT with a Modified Administered Activity Protocol in NETs of Variable Origin - A Phase 2 Registry Study.

Background: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs).

Objective: This study reports the adverse events (AEs) observed with patient-tailored administered activity.

Methods: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE.

Survival predictors of Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS).

Purpose: Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received Lu-Dotatate.

Methods: A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with Lu-Dotatate (four induction cycles of 5.

Efficacy of Lu-Dotatate Induction and Maintenance Therapy of Various Types of Neuroendocrine Tumors: A Phase II Registry Study.

Peptide receptor radionuclide therapy (PRRT) has been recently established as a treatment option for progressive gastro-entero-pancreatic neuroendocrine tumors (NETs) including four 200 mCi induction cycles. The purpose of this phase 2 trial is to expand use of PRRT to different types of NETs with the application of dose adjustment and evaluate value of maintenance therapy in patients who had disease control on induction therapy. Forty-seven PRRT naïve NET patients with different primary origin received Lu-DOTATATE induction therapy, ranging from 75 to 150 mCi per cycle, based on patients' clinical status such as liver and renal function, extent of metastases, and previous therapies.

It's a small world after all: A Canadian resident's perspective on COVID-19.

COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.

Stabilization of protein structure through π-π interaction in the second coordination sphere of pseudoazurin.

Noncovalent, weak interactions in the second coordination sphere of the copper active site of Pseudoazurin (PAz) from Achromobacter cycloclastes were examined using a series of Met16X variants. In this study, the differences in protein stability due to the changes in the nature of the 16th amino acid (Met, Phe, Val, Ile) were investigated by electrospray ionization mass spectrometry (ESI-MS) and far-UV circular dichroism (CD) as a result of acid denaturation. The percentage of native states (folded holo forms) of Met16Phe variants was estimated to be 75% at pH 2.

Challenging conventional wisdom: single domain metallothioneins.

Metallothioneins (MT) are a family of small cysteine rich proteins that have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as metallochaperones are undoubtedly involved in the homeostasis of both essential zinc and copper. While complete details of all possible cellular functions are still unknown, it is clear that they must be directly related to both the accessibility and the metal-binding properties of the many cysteine residues in the protein. The most well studied MTs are of mammalian origin and consist of two domains: a β-domain with 9 cysteine residues that sequesters 3 Cd(2+), 3 Zn(2+) or 6 Cu(+) ions, and an α-domain with 11 cysteine residues that sequesters 4 Cd(2+), 4 Zn(2+) or 6 Cu(+) ions.

Single-domain metallothioneins: evidence of the onset of clustered metal binding domains in Zn-rhMT 1a.

Mammalian metallothioneins bind up to seven Zn(2+) ions in two distinct domains: an N-terminal β-domain that binds three Zn(2+) ions and a C-terminal α-domain that binds four Zn(2+) ions. Domain specificity has been invoked in the metalation mechanism with cluster formation and bridging of the 20 Cys residues taking place prior to saturation with seven Zn(2+) ions. We report a novel experiment that examines Zn(2+) metalation by exploiting the expected decrease in K(F) at the onset of clustering using electrospray ionization mass spectrometry (ESI-MS).

Modeling the Zn(2+) and Cd(2+) metalation mechanism in mammalian metallothionein 1a.

Mammalian metallothioneins (MTs) are a family of small cysteine rich proteins believed to have a number of physiological functions, including both metal ion homeostasis and toxic metal detoxification. Mammalian MTs bind 7 Zn(2+) or Cd(2+) ions into two distinct domains: an N-terminal β-domain that binds 3 Zn(2+) or Cd(2+), and a C-terminal α-domain that binds 4 Zn(2+) or Cd(2+). Although stepwise metalation to the saturated M(7)-MT (where M=Zn(2+) or Cd(2+)) species would be expected to take place via a noncooperative mechanism involving the 20 cysteine thiolate ligands, literature reports suggest a cooperative mechanism involving cluster formation prior to saturation of the protein.

Noncooperative metalation of metallothionein 1a and its isolated domains with zinc.

Mammalian metallothioneins (MTs) are a family of small cysteine-rich proteins capable of binding 7 Zn(2+) or Cd(2+) ions into two distinct domains: an N-terminal β-domain that binds 3 Zn(2+) or Cd(2+) and a C-terminal α-domain that binds 4 Zn(2+) or Cd(2+). MT has been implicated in a number of physiological functions, including metal ion homeostasis, toxic metal detoxification, and as a protective agent against oxidative stress. Conventionally, MT has been understood to coordinate metal ions in a cooperative fashion.

Single domain metallothioneins: supermetalation of human MT 1a.

Metallothioneins are a family of small, cysteine rich proteins that have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as metallochaperones involved in the homeostasis of both essential zinc and copper. We report that human metallothionein 1a, well-known to coordinate 7 Zn(2+) or Cd(2+) ions with 20 cysteinyl thiols, will bind 8 structurally significant Cd(2+) ions, leading to the formation of the supermetalated Cd(8)-βα-rhMT 1a species, for which the structure is a novel single domain. ESI-mass spectrometry was used to determine the exact metalation status of the βα-rhMT.

Metal selectivity of the Escherichia coli nickel metallochaperone, SlyD.

SlyD is a Ni(II)-binding protein that contributes to nickel homeostasis in Escherichia coli. The C-terminal domain of SlyD contains a rich variety of metal-binding amino acids, suggesting broader metal binding capabilities, and previous work demonstrated that the protein can coordinate several types of first-row transition metals. However, the binding of SlyD to metals other than Ni(II) has not been previously characterized.

The "magic numbers" of metallothionein.

Metallothioneins (MT) are a family of small cysteine rich proteins, which since their discovery in 1957, have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as a metallochaperone involved in the homeostasis of both zinc and copper. The most well studied member of the family is the mammalian metallothionein, which consists of two domains: a β-domain with 9 cysteine residues, which sequesters 3 Cd(2+) or Zn(2+) or 6 Cu(+) ions, and an α-domain with 11 cysteine residues and, which sequesters 4 Cd(2+) or Zn(2+) or 6 Cu(+) ions. Despite over half a century of research, the exact functions of MT are still unknown.

Supermetalation of the beta domain of human metallothionein 1a.

Metallothionein has been implicated in a number of functions, including toxic metal detoxification, as a metal chaperone and in metal ion homeostasis. In this paper, we demonstrate that the beta domain of human metallothionein 1a, well-known to bind three Zn(2+) or Cd(2+) ions with nine cysteinyl sulfurs, is also capable of binding an additional Cd(2+) ion, leading to the formation of the supermetalated Cd(4)-beta-rhMT 1a. This intermediate, either by itself or in concert with the alpha domain of human metallothionein, is a likely model for metal exchange with the apoenzyme, which is one of the key roles of metallothionein.

Cu(I) binding properties of a designed metalloprotein.

The Cu(I) binding properties of the designed peptide C16C19-GGY are reported. This peptide was designed to form an alpha-helical coiled-coil but modified to incorporate a Cys-X-X-Cys metal-binding motif along its hydrophobic face. Absorption, emission, electrospray ionization mass spectrometry (ESI-MS), and circular dichroism (CD) experiments show that a 1:1 Cu-peptide complex is formed when Cu(I) is initially added to a solution of the monomeric peptide.

The Ni(II)-binding properties of the metallochaperone SlyD.

Metallochaperones are essential for the safe and targeted delivery of necessary yet toxic metal cofactors to their respective protein partners. In this study we examine the nickel-binding properties of the Escherichia coli protein SlyD, a factor that contributes to optimal nickel accumulation in this organism. This protein is also required for E.

Noncooperative cadmium(II) binding to human metallothionein 1a.

The two-domain (beta alpha) mammalian metallothionein binds seven divalent metals, however, the binding mechanism is not well characterized and recent reports require the presence of the partially metallated protein. In this paper, step-wise metallation of the metal-free, two-domain beta alpha-rhMT and the isolated beta-rhMT using Cd(II) is shown to proceed in a noncooperative manner by analysis of electrospray ionization mass spectrometric data. Under limiting amounts of Cd(II), all intermediate metallation states up to the fully metallated Cd(3)-beta-rhMT and Cd(7)-beta alpha-rhMT were observed.