Leuprolide

Key findings (each cites a source)

• A preclinical study reported synthesis and radiolabeling of a DOTA-coupled 9-amino-acid leuprolide peptide with 68Ga and 177Lu, with identity/purity validation by mass spectrometry and HPLC, and evaluation of tumor binding and imaging in breast cancer models. [PMID 35325547]
• In the same preclinical study, research investigated in vitro binding (reported nanomolar binding potency) across MCF7, T47D, and MDA-MB-231 breast cancer cell lines. [PMID 35325547]
• In nude mice xenograft models, the preclinical study reported that 68Ga-leuprolide showed rapid clearance from blood and low-to-moderate organ uptake, with reported uptake in an estrogen receptor-positive MCF7 tumor and favorable tumor-to-blood and tumor-to-muscle uptake ratios at a specified imaging timepoint. [PMID 35325547]
• The preclinical radiolabeled peptide study reported that the radiolabeled peptide was excreted primarily through the renal pathway. [PMID 35325547]
• A synthesis-focused study reported quick access to high-purity peptide drugs including a leuprolide analogue using heating-assisted liquid-phase peptide synthesis on a soluble polynorbornene support, reporting yields (56–77%) and purity (>95%) with short reaction times. [PMID 34823358]
• A PEGylation study reported synthesis of two PEGylated leuprolides of different molecular weight via NHS conjugation chemistry, with characterization by RP-HPLC (high purity), MALDI-MS (suggested 1:1 PEGylation), and 1H NMR (reaction on the imidazolyl group on histidine), and stability in pH 7.4 aqueous solutions. [PMID 31926774]
• The PEGylation study reported that PEGylated peptides could still counteract stimulatory action of androgens and mitogenic action of epidermal growth factor on cell proliferation in in vitro cell line assays. [PMID 31926774]
• In the PEGylation study, administration of the conjugates to male rats was reported to lead to an initial testosterone surge followed by suppression of testosterone secretion, and pharmacokinetic analyses reported prolonged circulating half-life, increased AUC, and decreased ClF for PEGylated drugs compared with unmodified peptide, after i.v. and s.c. administrations. [PMID 31926774]
• A formulation study evaluated the effect of taste-masking excipients (aspartame and menthol) on leuprolide suspension MDI performance, reporting differences in micronization/particle size-related metrics and mean ex-actuator dose, while reporting no significant effect on valve delivery and through-can dose uniformity. [PMID 11775953]
• In tracheostomized dogs in the formulation study, both formulations were reported to show comparable pharmacokinetic parameters and bioavailability, with the study concluding that taste-masking excipients did not affect lung absorption of leuprolide acetate. [PMID 11775953]
• A post hoc analysis of the EMBARK trial reported age-stratified results comparing regimens that included enzalutamide with leuprolide, enzalutamide alone, and leuprolide alone, reporting improvements in metastasis-free survival in the combination and monotherapy groups compared with leuprolide alone regardless of age group (<70 vs ≥70). [PMID 41274168]
• The EMBARK post hoc analysis reported that treatment-related serious adverse events and grade ≥3 adverse events were more common in patients aged ≥70 than in those <70 across treatment groups, while reporting that TRSAEs were low across age groups. [PMID 41274168]