Intraoperative Tumor Detection Using Pafolacianine
Abstract
:1. Introduction
2. FDA-Approved Pafolacianine for Intraoperative Ovarian Cancer Detection
3. Pafolacianine for the Detection of a Wide Variety of Malignancies during Surgery
3.1. Lung Cancer
3.2. Renal Cancer
3.3. Pituitary Tumors
3.4. Gastric Cancer
4. Pafolacianine in Comparison with Other Similar Agents Used for Intraoperative Molecular Imaging
5. Benefits and Limitations of Using Pafolacianine for Cancer Detection during Surgery
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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ClinicalTrials.gov | Study Title | Condition | Status | Locations |
---|---|---|---|---|
Ovarian cancer detection | ||||
NCT02317705 | Phase 2 Study of OTL38 for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer | Ovarian cancer | Completed | University of CA at Irvine, CA, USA; Moffitt Cancer Center Tampa, FL USA; Mayo Clinic, Rochester, MI, USA; University of Pennsylvania, PA, USA |
NCT03180307 | OTL38 for Intra-Operative Imaging of Folate Receptor Positive Ovarian Cancer | Ovarian cancer | Completed | The Mayo Clinic, Phoenix, AZ, USA; University of Arizona, Tucson, AZ, USA; City of Hope Medical Center; Duarte, CA, USA (and 8 others) |
NCT04941378 | OTL38 Injection (OTL38) for Intra-Operative Imaging of Folate Receptor Positive Ovarian Cancer | Ovarian cancer | Withdrawn | Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA |
Other cancers/diseases | ||||
NCT02602119 | Intraoperative Imaging of Pulmonary Nodules by OTL38 | Neoplasms | Completed | Hospital of the University of Pennsylvania, Philadelphia, PA, USA |
NCT03938701 | Fluorescence Imaging of Disease Activity in IBD and Rheumatoid Arthritis Using OTL38 | Inflammatory bowel disease, Rheumatoid arthritis | Not yet recruiting | University Medical Center Groningen, Netherlands |
NCT02872701 | OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules | Lung neoplasms | Completed | Beth Israel Deaconess Medical Center Boston, MA, USA; Cleveland Clinic Cleveland, OH, USA; University of Pennsylvania, Philadelphia, PA, USA (and 3 others) |
NCT02852252 | Solid Tumor Cancer Surgery with or without Intraoperative Imaging: A Registry | Bladder cancer, Gastric cancer | Completed | Hospital of the University of Pennsylvania, Philadelphia, PA, USA |
NCT04241315 | ELUCIDATE: Enabling Lung Cancer Identification Using Folate Receptor Targeting | Lung neoplasms, Lung cancer | Completed | Stamford, CT, US; University of Iowa, Iowa, USA; Beth Israel Deaconess Medical Center Boston, MA, USA (and 9 others) |
NCT02629549 | Intraoperative Imaging of Pituitary Adenomas by OTL | Neoplasms, Pituitary adenomas | Terminated | Hospital of the University of Pennsylvania, Philadelphia, PA, USA |
Agents Used for Intraoperative Molecular Imaging | Comments |
---|---|
5-Aminolevulinic acid | - It emits fluorescence in the visible spectrum, compared with pafolacianine, which emits fluorescence in the near-infrared spectrum [67]; - It provides an inferior depth of penetration and significantly higher background signal compared with pafolacianine [67]; - It is used predominantly for targeting bladder cancer [100] and malignant gliomas (approved by the FDA in 2017 for intraoperative molecular imaging in patients with suspected high-grade gliomas) [101]; - It requires patients to be protected from the sun and ultraviolet radiation for 24 hours after surgery, compared with pafolacianine, which does not limit patient activity or restrict discharge from the hospital [67]; - It may cause liver damage, chest pain, neuropathy, and sudden death [102], while pafolacianine shows minor side effects and no associated toxicity [6]. |
Folate-fluorescein isothiocyanate | - It exhibits fluorescence in the visible range, compared with pafolacianine, which emits fluorescence in the near-infrared spectrum [13]; - It overlaps with the absorption spectrum of hemoglobin, reducing the signal in a surgical field covered by blood [47]; - It binds FRα, having high specificity [60]; - It differs from pafolacianine in regard to the associated fluorochrome, the folate-fluorescein isothiocyanate carrying fluorescein, while pafolacianine carries an indocyanine green analogue called SO456; - It provides a higher background autofluorescence, inferior contrast, increased scattering, and limited tissue penetration than pafolacianine [91]; - It has significant patient safety advantages, with no associated toxicity [13]. |
Sodium fluorescein | - It can be visualized under visible light [103]; - It does not have a specific target, but its uptake in the cancer lesions can be estimated by the endothelial breakdown and high vascular permeability [103,104]; - It is safe, implying no toxicity [68]; - It provides a good contrast, but with an inferior depth of penetration [74,75]. |
Indocyanine green | - It is a near-infrared contrast agent [13]; - It is associated with a similar depth of detection and autofluorescence to pafolacianine, due to its decreased light spread and blood absorption [105,106]; - It does not have tumor specificity, and it may also accumulate in areas of inflammation, creating background autofluorescence [58]; - It maintains fluorescence for a couple of minutes, compared to pafolacianine, which exhibits fluorescence for hours [91,107]; - It exhibits few to no adverse reactions [13]. |
Criteria | Benefits | Limitations |
---|---|---|
Relatively new technology | Near-infrared imaging with pafolacianine is a relatively new technology, recently approved by the FDA for tumor detection in ovarian cancer patients, which has promising outcomes in terms of safety and efficacy [6]. | As a newly developed technique, it needs to be popularized among both surgeons and patients in order to reap the benefits of improved tumor detection. Hospitals also need to provide the necessary logistics to enable surgical procedures of this kind and to provide surgeons with special training on their use. |
Administration | Pafolacianine is intravenously administered within a couple of hours prior to the surgery [6]. In comparison with other targeted fluorophores that are administered up to 1 week before the surgery, pafolacianine seems to be efficient even when delivered just a few hours before resection [13]. | It is recommended to avoid the use of folate, folic acid, and folate-based supplements during the 48 h prior to pafolacianine administration [6]. |
Safety | Pafolacianine has a low toxicity profile, the most frequent side effects being dyspepsia, vomiting, nausea, abdominal pain, chest discomfort, flushing, pruritus, and hypersensitivity [6]. | It can lead to fetal harm when delivered to pregnant women [6]. |
Efficacy | Pafolacianine binds FRα with a ∼1 nM affinity, and it is cleared from tissues which do not express the receptor, with a half-time of <30 minutes. It is demonstrated that pafolacianine enables tumor detection at concentrations of less than 100-fold those needed to cause signs of toxicity [23]. It also provides excellent contrast against the healthy background and a long residence time in the malignant lesions. It exhibits extremely low autofluorescence and a great depth of penetration, with cancer lesions being visible up to 1 cm below the tissue surface [24,108,109,110]. Additionally, intraoperative imaging using pafolacianine provided a 2-fold improvement in surgeons’ ability to identify malignant lesions [4]. | Image interpretation errors may also occur, including both false negatives and false positives [6]. False positive errors can be produced due to pinolcaine’s binding of FRβ, overexpressed on the surface of the macrophages accumulated in the non-malignant regional lymph nodes [4]. |
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Dindere, M.E.; Tanca, A.; Rusu, M.; Liehn, E.A.; Bucur, O. Intraoperative Tumor Detection Using Pafolacianine. Int. J. Mol. Sci. 2022, 23, 12842. https://doi.org/10.3390/ijms232112842
Dindere ME, Tanca A, Rusu M, Liehn EA, Bucur O. Intraoperative Tumor Detection Using Pafolacianine. International Journal of Molecular Sciences. 2022; 23(21):12842. https://doi.org/10.3390/ijms232112842
Chicago/Turabian StyleDindere, Mihaela Elisabeta, Antoanela Tanca, Mihaela Rusu, Elisa Anamaria Liehn, and Octavian Bucur. 2022. "Intraoperative Tumor Detection Using Pafolacianine" International Journal of Molecular Sciences 23, no. 21: 12842. https://doi.org/10.3390/ijms232112842