Early Detection of Lung Cancer with Meso Tetra (4-Carboxyphenyl) Porphyrin-Labeled Sputum

Abstract

Introduction Early detection of lung cancer in high-risk individuals reduces mortality. Low-dose spiral computed tomography (LDCT) is the current standard but suffers from an exceedingly high false-positive rate (>96%) leading to unnecessary and potentially dangerous procedures. We, therefore, set out to develop a simple, noninvasive, and quantitative assay to detect lung cancer. Methods This proof-of-concept study evaluated the sensitivity/specificity of the CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphe-nyl) porphyrin (TCPP)-labeled lung sputum samples and subjects’ baseline characteristics were assessed for their predictive power by multivariable logistic regression. A receiver operating characteristic curve was constructed to evaluate the sensitivity/specificity of the CyPath assay. Results RFCs were detectable in cancer subjects more often than in high-risk ones (p = 0.015), and their characteristics differed between cohorts. Two independent predictors of cancer were the mean of RFC average fluorescence intensity/area per subject (p < 0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall accuracy of 81% in the test population; false-positive rate of 40% and negative predictive value of 83%. Conclusions The tetra (4-carboxyphenyl) porphyrin-based CyPath assay correctly classified study participants into cancer or high-risk cohorts with considerable accuracy. Optimizing sputum collection, sample reading, and refining the classifier should improve sensitivity and specificity. The CyPath assay thus has the potential to complement LDCT screening or serve as a stand-alone approach for early lung cancer detection.

Zr-MOFs Integrated with a Guest Capturer and a Photosensitizer for the Simultaneous Adsorption and Degradation of 4-Chlorophenol

“…The content of TCPP(Pd) was quantified to be 15 μmol TCPP(Pd) per gram 2.5CMCD@ NU-1000-0.5TCPP(Pd) through the standard curve method (Figure S13). 57,58 Subsequently, the photodegradation performance of 2.5CMCD@NU-1000-0.5TCPP(Pd) toward 4-CP was investigated under a red LED lamp. As shown in Figure 5A, the adsorbed 4-CP shows a characteristic UV−vis peak at 280 nm (black line).…”

“…The content of TCPP­(Pd) was quantified to be 15 μmol TCPP­(Pd) per gram 2.5CMCD@NU-1000-0.5TCPP­(Pd) through the standard curve method (Figure S13). , …”

Identification of a novel mechanism for meso‐tetra (4‐carboxyphenyl) porphyrin (TCPP) uptake in cancer cells

“…Thus, the tumor microenvironment may play an important role in elucidating the tumor‐localizing properties of TCPP. A more comprehensive understanding of interactions between specific porphyrins, cancer cells, and cancer‐associated cells may help improve several oncology‐related technologies, including the development of porphyrin‐drug conjugates as highly specific drug‐delivery vehicles for tumor tissue, 96,97 the use of porphyrins for the identification of tumor margins for surgical resection 98 and the development of improved porphyrins for cancer diagnostics 2 …”

“…Porphyrins are organic compounds with a basic structure of four pyrroles and, in some cases, a coordinated metal ion. Porphyrins have long been known to have an affinity for neoplastic tissue, 1 which has led to their use in cancer diagnostics 2‐4 and cancer therapeutics such as photodynamic therapy (PDT) 5‐7 . PDT causes cellular damage through the generation of oxygen radicals when photosensitizing agents are exposed to light 8 .…”

“…TCPP has been shown to accumulate in tumor cells 30,31 and is highly fluorescent, 32 which makes it an especially attractive agent for cancer diagnostics. As demonstrated by Patriquin et al in a clinical trial for the early detection of lung cancer in sputum cells, TCPP labeling of sputum cells can distinguish samples from high‐risk patients with lung cancer from those without the disease with 81% accuracy 2 . Very little is known about the molecular basis of TCPP’s tissue/tumor specificity, how TCPP enters cells, and where TCPP locates once in the cell.…”