Mn-labelled Beta-cyclodextrin for Melanoma Imaging: A Proof-of-concept Preclinical Study.

Background/aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled (Mn) randomly methylated beta-cyclodextrin ([Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [Ga]Ga-DOTA-NAPamide and PGE2 selective [Ga]Ga-DOTAGA-RAMEB cyclodextrin.

Materials And Methods: Post-injection of [Ga]Ga-DOTA-NAPamide, [Ga]Ga-DOTAGA-RAMEB, and [Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter.

Diagnosis of Melanoma with Cu-Labeled PET Tracer.

Until the recent years, substances containing radioactive Cu were strongly considered as potential positron-emitting radiopharmaceuticals for use in positron emission tomography (PET) applications; however, due to their suitably long half-life, and generator-independent and cost-effective production, they seem to be economically viable for human imaging. Since malignant melanoma (MM) is a major public health problem, its early diagnosis is a crucial contributor to long-term survival, which can be achieved using radiolabeled α-melanocyte-stimulating hormone analog NAPamide derivatives. Here, we report on the physicochemical features of a new CB-15aneN-based Cu(II) complex ([Cu(KFTGdiac)]) and the and characterization of its NAPamide conjugate.

[Mn]Mn-BPPA-Trastuzumab: A Promising HER2-Specific PET Radiotracer.

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [Mn]Mn isotope.

Investigation of the Effect on the Albumin Binding Moiety for the Pharmacokinetic Properties of Ga-, Bi-, and Lu-Labeled NAPamide-Based Radiopharmaceuticals.

Although radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radiolabeled DOTA-NAPamide compounds by incorporating a 4-(p-iodo-phenyl)-butanoic acid (IPB) into the molecules. Followed by Ga-, Bi-, and Lu-labelling, the radiopharmaceuticals ([Ga]Ga-DOTA-IPB-NAPamide, [Bi]Bi-DOTA-IPB-NAPamide, [Lu]Lu-DOTA-IPB-NAPamide) were characterized in vitro.