Evaluation of 177Lu and 47Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry.
Mol Pharm
; 18(12): 4511-4519, 2021 12 06.
Article
in En
| MEDLINE
| ID: mdl-34714082
ABSTRACT
Lu-177-based, targeted radiotherapeutics/endoradiotherapies are an emerging clinical tool for the management of various cancers. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) remains the workhorse for such applications but can limit apparent molar activity or efficient charge modulation, which can impact target binding and, as a consequence, target efficacy. Previously, our lab had developed the small, rare earth selective bifunctional chelator, picaga, as an efficient bifunctional chelator for scandium and lutetium isotopes. Here, we assess the performance of these constructs for therapy in prostate-specific membrane antigen (PSMA)-expressing tumor xenografts. To assess the viability of picaga conjugates in conjunction with long in vivo circulation, a picaga conjugate functionalized with a serum albumin binding moiety, 177Lu-picaga-Alb53-PSMA, was also synthesized. A directly comparative, low, single 3.7 MBq dose treatment study with Lu-PSMA-617 was conducted. Treatment with 177Lu-picaga-Alb53-PSMA resulted in tumor regression and lengthened median survival (54 days) when compared with the vehicle (16 days), 47Sc-picaga-DUPA-, 177Lu-picaga-DUPA-, and 177Lu-PSMA-617-treated cohorts (21, 23, and 21 days, respectively).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
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Radioisotopes
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Scandium
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Chelating Agents
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Prostate-Specific Antigen
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Radiopharmaceuticals
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Dipeptides
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Heterocyclic Compounds, 1-Ring
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Lutetium
Type of study:
Evaluation_studies
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Mol Pharm
Journal subject:
BIOLOGIA MOLECULAR
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FARMACIA
/
FARMACOLOGIA
Year:
2021
Document type:
Article
Affiliation country: