Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations

Denora, Nunzio; Lopedota, Angela; Candia, Modesto de; Cellamare, Saverio; Degennaro, Leonardo; Luisi, Renzo; Mele, Antonietta; Tricarico, Domenico; Cutrignelli, Annalisa; Laquintana, Valentino; Altomare, Cosimo; Franco, Massimo; Dimiccoli, Vincenzo; Tolomeo, Anna; Scilimati, Antonio

doi:10.1016/j.ejps.2016.10.001

Cited by 7 publications

(15 citation statements)

References 16 publications

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“…To possibly overcome the disadvantages related to IASOdopa ® injectable solution, , Denora et al developed an innovative formulation of [ 18 F]F-DOPA in a sterile solution of lactate at pH 5.0, which guaranteed a significant improvement of the drug chemical stability. This pH value is compatible with the direct infusion and conferred longer shelf lives than the one reported for the commercial product [ 26 , 64 ].…”

Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 75%

“…Clinical trials involving L-DOPA in PD have significantly influenced the development of new PET tracers for understanding the role and metabolism of DA in this disorder. L-DOPA chemical analogues as tracers ( Figure 2 ), and their injectable stable formulations have been developed and evaluated to assess DA turnover [ 26 , 64 ].…”

Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 99%

“…Among these approaches, we focused on several examples of imaging agents developed by Italian research groups (Table 1). [27] Conjugation of an albumin derivative with a DOTA ring 177 Lu, 111 In, 64 Cu PET Radio-guided occult lesion localization In vivo: female adult rats [28] Conjugation of a VCAM-1-binding peptide with a DOTA ring; development of a biotin/avidin three-step pretargeting system based on the same VCAM-1-binding peptide 68…”

Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 99%

“…The radiolabeling of HAC with Lutetium-177 ( 177 Lu) and Indium-111 ( 111 In) yielded products with high RCP and stability to radiolysis in saline suspension for at least 6 days after labeling. For in vivo studies, HAC was labeled with the positron-emitter Copper-64 ( 64 Cu); 64 Cu-HAC was tested on adult female rats by using a µPET/CT system, evidencing that the tracer remained located in the mammary glands for 40 h without spreading in healthy tissues or being drained by the lymphatic circulation (Figure 4). These preliminary studies highlighted that this new albumin derivative, labeled with 177 Lu or 111 In, might improve the efficacy and safety of the ROLL procedures; moreover, the low-penetrating beta particles emitted by 177 Lu might be exploited for destroying tumor cells surrounding the lesion.…”

Section: Polysaccharide-and Albumin-based Conjugates For Nuclear Imagingmentioning

confidence: 99%

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The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

et al. 2021

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Many modern therapeutic approaches are based on precise diagnostic evidence, where imaging procedures play an essential role. To date, in the diagnostic field, a plethora of agents have been investigated to increase the selectivity and sensitivity of diagnosis. However, the most common drawbacks of conventional imaging agents reside in their non-specificity, short imaging time, instability, and toxicity. Moreover, routinely used diagnostic agents have low molecular weights and consequently a rapid clearance and renal excretion, and this represents a limitation if long-lasting imaging analyses are to be conducted. Thus, the development of new agents for in vivo diagnostics requires not only a deep knowledge of the physical principles of the imaging techniques and of the physiopathological aspects of the disease but also of the relative pharmaceutical and biopharmaceutical requirements. In this scenario, skills in pharmaceutical technology have become highly indispensable in order to respond to these needs. This review specifically aims to collect examples of newly developed diagnostic agents connoting the importance of an appropriate formulation study for the realization of effective products. Within the context of pharmaceutical technology research in Italy, several groups have developed and patented promising agents for fluorescence and radioactive imaging, the most relevant of which are described hereafter.

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Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 75%

Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 99%

Section: Main Technological Strategies and Examples Of Imaging Agents Developed For Improving Diagnostic Efficiencymentioning

confidence: 99%

Section: Polysaccharide-and Albumin-based Conjugates For Nuclear Imagingmentioning

confidence: 99%

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The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

et al. 2021

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“…Other possible applications include psychiatric [5,6] and age-related neurodegenerative disorder diagnoses [7]. Figure 1)-is a positron emission tomography (PET) diagnostic radiotracer [1,2], useful to detect pathological loss of dopaminergic neuron terminals in the striatum. Thus, 6-[ 18 F]fluoro-L-DOPA is used for the diagnosis of Parkinson′s disease (PD) and distinction between essential tremor and parkinsonian syndromes (PS), especially at the PS onset [3].…”

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confidence: 99%

(S)-Ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylenedioxyphenyl)propanoate

Lentini

Cavalluzzi

Degennaro

et al. 2019

Molbank

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A multistep gram-scale synthesis of (S)-ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylenedioxyphenyl)propanoate (2) has been developed. The title compound was prepared starting from commercially available l-DOPA which was O- and N-protected before undergoing iodination by CF3CO2Ag/I2. The structure of the target compound was confirmed using IR, 1H-NMR, 13C-NMR, 2D (COSY, HSQC) NMR spectroscopy, as well as ESI-MS and HRMS.

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Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson’s Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods

Uygur,

Karatay,

Derviş

et al. 2024

Mol Neurobiol

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Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography–mass spectrometry (LC–MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague–Dawley rats and a Parkinson’s disease experimental model to evaluate the compounds’ bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.

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Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations

Cited by 7 publications

References 16 publications

The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

(S)-Ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylenedioxyphenyl)propanoate

Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson’s Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods

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