Pafolacianine (OTL-0038; OTL-38; Cytalux)   中文名称: 帕弗拉辛纳

Absorption, Distribution and Excretion
The mean Cmax of pafolacianine was 59.1 ± 5.94 ng/mL and AUCinf was 63.6 ± 12.6 ng x hr/mL.
Following a single intravenous infusion of radiolabeled pafolacianine sodium, approximately 35% of the dose was recovered in urine (19.1%) and in feces (15.8%) after approximately 3-5 weeks.
The mean volume of distribution (V_z) is 17.1 ± 5.99 L, indicating distribution into tissues. During intraoperative molecular imaging for surgically resectable pulmonary adenocarcinoma, pafolacianine accumulated in nearly 70% of squamous cell carcinomas.
The mean plasma clearance is 28.6 ± 4.97 L/hr.

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Metabolism / Metabolites
The metabolism of pafolacianine is unknown; however, pafolacianine is not metabolized by cytochrome P450 (CYP) enzymes.

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Biological Half-Life
The elimination half-life of pafolacianine is 0.44 ± 0.23 hours.

Protein Binding
Plasma protein binding of pafolacianine is 93.7%. No notable partitioning into red blood cells was observed.

[1]. Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model. Cancer. 2017 May 15;123(6):1051-1060.

Pafolacianine, or OTL38, is a folate analogue conjugated with a fluorescent dye that absorbs light in the near-infrared (NIR) spectrum within a range of 760 nm to 785 nm, with a peak absorption of 776 nm. It emits fluorescence within a range of 790 nm to 815 nm with a peak emission of 796 nm. The longer wavelength allows for deeper penetration of the fluorescent light through tissues for better imaging and detection of tumours. Pafolacianine targets the folate receptor alpha (FRα) which is upregulated in numerous epithelial malignancies. On November 29, 2021, the FDA approved pafolacianine as an adjunct imaging agent for intraoperative identification of malignant lesions in adult patients with ovarian cancer. It is currently under investigation for use in FRα-positive pituitary adenoma, lung cancer, and renal-cell carcinoma, which is thought to be the second-highest folate receptor-expressing cancer.
Pafolacianine is a fluorescent imaging agent composed of a folate receptor-alpha (FRa)-targeting ligand conjugated to a fluorescent near infrared (NIR) dye, that can be used for imaging of FRa-expressing tumor cells. Upon administration, the FRa-targeting moiety of pafolacianine specifically binds to FRa expressed on tumor cells thus selectively delivering the fluorescent dye to FRa-expressing tumor cells. Upon NIR imaging, tumor cells fluoresce, which allows for the visualization and identification of FRa-overexpressing tumor cells. FRa, a high-affinity folate-binding protein and a member of the folate receptor family, is overexpressed in various cancer cell types.
See also: Pafolacianine Sodium (active moiety of).

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Drug Indication
Pafolacianine is an optical imaging agent indicated in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions.

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Mechanism of Action
Pafolacianine is consists of folic acid linked by its γ-carboxyl and a short spacer to an indocyanine green-related near-infrared dye called SO456. It is used for intraoperative fluorescence for tumour identification and surgical resection. It targets the folate receptor alpha (FRα), which is often overexpressed in various cancers including ovarian cancer. Pafolacianine binds to FRα-expressing cancer cells with an affinity of ~1 nM and is internalized via receptor-mediated endocytosis to be concentrated in FR-positive cancer tissues. Pafolacianine absorbs light and in the near-infrared (NIR) region within a range of 760 nm to 785 nm with a peak absorption of 776 nm and, upon excitation, emits fluorescence within a range of 790 nm to 815 nm with a peak emission of 796 nm.

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Pharmacodynamics
Tumor to background ratios changed with different mass doses studied. High tumor to background ratio was observed with 0.025 mg/kg dose. Pafolacianine exposure-response relationships and the time course of pharmacodynamic responses are unknown.

C61H67N9O17S4

1326.4948

1325.353

1628423-76-6

1628858-03-6 (sodium);1628423-76-6 (free acid);

135565623

Green to dark green solid powder

4

441

8

22

24

91

3330

1

S(C1C([H])=C([H])C2=C(C=1[H])C(C([H])([H])[H])(C([H])([H])[H])/C(=C(/[H])\C(\[H])=C1\C(=C(C([H])([H])C([H])([H])C\1([H])[H])/C(/[H])=C(\[H])/C1C(C([H])([H])[H])(C([H])([H])[H])C3C([H])=C(C([H])=C([H])C=3[N+]=1C([H])([H])C([H])([H])C([H])([H])C([H])([H])S(=O)(=O)O[H])S(=O)(=O)[O-])OC1C([H])=C([H])C(C([H])([H])[C@@]([H])(C(=O)O[H])N([H])C(C3C([H])=C([H])C(=C([H])C=3[H])N([H])C([H])([H])C3=C([H])N=C4C(C(N([H])C(N([H])[H])=N4)=O)=N3)=O)=C([H])C=1[H])/N2C([H])([H])C([H])([H])C([H])([H])C([H])([H])S(=O)(=O)O[H])(=O)(=O)O[H]

PDXNSXLPXJFETD-DYVQZXGMSA-N

InChI=1S/C61H67N9O17S4/c1-60(2)46-33-44(90(81,82)83)22-24-49(46)69(28-5-7-30-88(75,76)77)51(60)26-16-38-10-9-11-39(17-27-52-61(3,4)47-34-45(91(84,85)86)23-25-50(47)70(52)29-6-8-31-89(78,79)80)54(38)87-43-20-12-37(13-21-43)32-48(58(73)74)66-56(71)40-14-18-41(19-15-40)63-35-42-36-64-55-53(65-42)57(72)68-59(62)67-55/h12-27,33-34,36,48H,5-11,28-32,35H2,1-4H3,(H9-,62,63,64,66,67,68,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86)/t48-/m0/s1

hydrogen (S)-2-(4-(((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl)amino)benzamido)-3-(4-(((E)-2-((E)-2-(3,3-dimethyl-5-sulfonato-1-(4-sulfonatobutyl)-3H-indol-1-ium-2-yl)vinyl)-6-(2-((E)-3,3-dimethyl-5-sulfonato-1-(4-sulfonatobutyl)indolin-2-ylidene)ethylidene)cyclohex-1-en-1-yl)oxy)phenyl)propanoate

OTL0038 OTL-38OTL 0038 OTL 38OTL-0038 OTL38 Cytalux

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~25 mg/mL (~18.85 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (1.57 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.08 mg/mL (1.57 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。