Advances in PSMA theranostics

Jeitner, Thomas M.; Babich, John W.; Kelly, James M.

doi:10.1016/j.tranon.2022.101450

Cited by 29 publications

(30 citation statements)

References 265 publications

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“…Preparation of Lyophilized Kits. A single vial kit containing a lyophilized precursor, either P17-087 (4) or P17-088 (7), was prepared. The kits were prepared with the following formulation: 100 μg of ligand 4 or 7, 136 mg of sodium acetate trihydrate, and 8 mg of NaOH.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Ascorbic acid (100 mg) was also added in each kit to suppress radiolysis. After lyophilization, slightly yellow cakes were obtained for both P17-087 (4) or P17-088 (7), and the color originates from the added ascorbic acid. These kits were rapidly and efficiently labeled with [ 177 Lu]Lu(III).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…48,50−55 In addition to 177 Lucomplexes, DOTA and its derivatives also form stable complexes with a variety of useful metal radionuclides, such as Ga-68, In-111, Sc-44, Sc-47, Y −90 , Tb-161, Ac-225, Bi-213, Tb-149, or Pb-212. 7,24,30 Described herein is the synthesis, radiolabeling, and characterization of DOTA(GA) 2 conjugated agents, [ 177 Lu]Lu-4 and [ 177 Lu]Lu-7, for PSMA-targeting radionuclide therapy in prostate cancer patients. Biological properties for PSMA-targeting were investigated.…”

Section: ■ Introductionmentioning

confidence: 99%

“…New PSMA-targeting radioligands modified with the albumin binding group showing enhanced blood circulation may provide additional advantages. Derivatives of [ 177 Lu]Lu-PSMA-617 containing an albumin binding group, such as Evans Blue , or p -iodophenylbutanoyl group − showed considerably increased accumulation in the tumor, which could correlate with better therapeutic outcomes in clinical settings. ,− In addition to 177 Lu-complexes, DOTA and its derivatives also form stable complexes with a variety of useful metal radionuclides, such as Ga-68, In-111, Sc-44, Sc-47, Y –90 , Tb-161, Ac-225, Bi-213, Tb-149, or Pb-212. ,, …”

Section: Introductionmentioning

confidence: 99%

“…NMR and LC-HRMS of P17−087 (4) and P17-088(7) (Figures S1−S4); LC-HRMS of [ nat Lu]Lu-4 ([ nat Lu]Lu-P17-087) and [ nat Lu]Lu-7 ([ nat Lu]Lu-P17-088) (Figures S5 and S6); in vitro stability of [ 177 Lu]Lu-4 and [ 177 Lu]Lu-7 (Figures S7 and S8); ex vivo metabolism of [ 177 Lu]Lu-7 (Figures S9−S11); cell uptake studies of [ 177 Lu]Lu-4, [ 177 Lu]Lu-7 and [ 177 Lu]Lu-PSMA-617: (Tables S1 and S2); biodistribution of [ 177 Lu]Lu-4, [ 177 Lu]Lu-7 and [ 177 Lu]Lu-PSMA-617: in nude mice with PSMA+ and PSMA-tumor model (TablesS3−S5); dosimetry calculation of [177 Lu]Lu-4 (includes biological clearance where data could be fitted to 2 exponentials + skin added to remainder) (TableS6); and dosimetry calculation of [177 Lu]Lu-7 (includes biological clearance where data could be fitted to 2 exponentials + skin added to remainder) (TableS7) (PDF)Molecular formula strings (CSV) h i b i t e d .…”

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New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177)

Zha¹,

Choi²,

et al. 2022

J. Med. Chem.

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Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported 68Ga-imaging agent, [68Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA)2 led to P17-087 (4) and P17-088 (7). Both agents showed excellent PSMA binding affinity (IC50 = 10–30 nM) comparable to that of recently FDA-approved [177Lu]Lu-PSMA-617 (Pluvicto). Biodistribution studies in PSMA expressing tumor bearing mice showed that [177Lu]Lu-4 exhibited very high tumor uptake and a fast blood clearance similar to those of [177Lu]Lu-PSMA-617. Conversely, [177Lu]Lu-7, containing an albumin binder, extended its blood half-life and exhibited significantly higher uptake and longer tumor residence time than [177Lu]Lu-4 and [177Lu]Lu-PSMA-617. The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177)

Zha¹,

Choi²,

et al. 2022

J. Med. Chem.

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Applications of radiolabeled antibodies in neuroscience and neuro‐oncology

Pakula

Scott

2023

Labelled Comp Radiopharmac

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Positron emission tomography (PET) is a powerful tool in medicine and drug development, allowing for non‐invasive imaging and quantitation of biological processes in live organisms. Targets are often probed with small molecules, but antibody‐based PET is expanding because of many benefits, including ease of design of new antibodies toward targets, as well as the very strong affinities that can be expected. Application of antibodies to PET imaging of targets in the central nervous system (CNS) is a particularly nascent field, but one with tremendous potential. In this review, we discuss the growth of PET in imaging of CNS targets, present the promises and progress in antibody‐based CNS PET, explore challenges faced by the field, and discuss questions that this promising approach will need to answer moving forward for imaging and perhaps even radiotherapy.

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