Absorption, Distribution and Excretion
The mean Cmax of pafforacinin was 59.1 ± 5.94 ng/mL, and the AUCinf was 63.6 ± 12.6 ng·hr/mL. Following a single intravenous infusion of radiolabeled pafforacinin sodium, approximately 35% of the dose was recovered from urine (19.1%) and feces (15.8%) after 3–5 weeks. The mean volume of distribution (V_z) was 17.1 ± 5.99 L, indicating drug distribution in tissues. Intraoperative molecular imaging of surgically resectable lung adenocarcinoma revealed pafforacinin accumulation in nearly 70% of squamous cell carcinomas. The mean plasma clearance was 28.6 ± 4.97 L/hr.

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Metabolism/Metabolites
The metabolic pathway of palvastatin is not well understood; however, palvastatin is not metabolized by cytochrome P450 (CYP) enzymes.

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

Protein Binding
Pafratinine had a plasma protein binding rate of 93.7%. No significant erythrocyte partitioning 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 (also known as OTL38) is a folic acid analog conjugated with a fluorescent dye. It absorbs light in the near-infrared (NIR) spectral range of 760 nm to 785 nm, with an absorption peak at 776 nm. Its fluorescence emission wavelength ranges from 790 nm to 815 nm, with an emission peak at 796 nm. The longer wavelengths allow the fluorescence to penetrate deeper into tissues, resulting in better imaging and detection of tumors. Pafolacianine targets folate receptor α (FRα), which is upregulated in various epithelial malignancies. On November 29, 2021, the U.S. Food and Drug Administration (FDA) approved pavlacianine as an adjunct imaging agent for intraoperative identification of malignant lesions in adult ovarian cancer patients. Currently, pavlacianine is being investigated for the treatment of FRα-positive pituitary adenomas, lung cancer, and renal cell carcinoma, with renal cell carcinoma considered the second most frequently expressed cancer of the folate receptor.
Paporaciline is a fluorescent imaging agent composed of a ligand targeting folate receptor α (FRα) coupled to a near-infrared (NIR) fluorescent dye, used for imaging tumor cells expressing FRα. After administration, the FRα-targeting portion of paporaciline specifically binds to FRα expressed on the surface of tumor cells, selectively delivering the fluorescent dye to FRα-expressing tumor cells. Through near-infrared imaging, the tumor cells fluoresce, allowing observation and identification of FRα-overexpressing tumor cells. Folate receptor α (FRα) is a high-affinity folate-binding protein, a member of the folate receptor family, and is overexpressed in various cancer cell types.
See also: Pafraciline Sodium (active ingredient).
Pharmaceutical Indications

Paporaciline is an optical imaging agent indicated for use in adult patients with ovarian cancer as an adjunct to intraoperative identification of malignant lesions.
Mechanism of Action Pafraxinin is composed of folic acid linked to an indocyanine green-associated near-infrared dye, SO456, via its γ-carboxyl group and a short spacer. It is used for intraoperative fluorescence imaging to identify tumors and facilitate surgical resection. Its target is the folic acid receptor α (FRα), which is frequently overexpressed in various cancers, including ovarian cancer. Pafraxinin has an affinity of approximately 1 nM for FRα-expressing cancer cells and enters cells via receptor-mediated endocytosis, accumulating in FR-positive cancer tissues. Pafraxinin absorbs light in the near-infrared (NIR) region from 760 nm to 785 nm, with an absorption peak at 776 nm; upon excitation, it emits fluorescence in the range of 790 nm to 815 nm, with an emission peak at 796 nm. Pharmacodynamics The tumor-to-background concentration ratio varies with different doses. A higher tumor-to-background concentration ratio was observed at a dose of 0.025 mg/kg. The exposure-response relationship and time course of pharmacodynamic response of pfracinine are unclear.

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

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

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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)

Solubility in Formulation 1: ≥ 2.08 mg/mL (1.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.08 mg/mL (1.57 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)