Page 38 - ARNM-2-3

Advances in Radiotherapy
& Nuclear Medicine Molecular imaging of lung cancer

MRI detected early-stage primary pulmonary tumors in MRI to distinguish benign lung tumors from malignant
a human study involving 21 NSCLC patients. Moreover, ones, as well as adenocarcinoma from squamous cell
T1W and T2W MRI were able to assess the heterogeneity carcinoma. 102,103 Investigational superparamagnetic iron
and biological behaviors that correlated with lung oxide nanoparticle-based MRI contrast agents have also
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cancer stage. In preclinical settings, lung MRI has been been reported to detect lung tumor nodules in a mouse
developed as a standard protocol to longitudinally monitor study using T2W MRI. 104
mouse lung tumor progression and regression using T1W To efficiently and precisely improve the early detection
and T2W imaging. 47,87 A combination of T1W, T2W, and of lung cancer with higher specificity and sensitivity,
DW MRI has repeatedly shown equivalent or superior molecularly targeted probes have been engineered by
lung nodule detection capability compared to CT or FDG- combining MRI contrast agents with biomarker-targeting
PET. 27,76,82,83,88,89 moieties. Although no molecular targeting MRI contrast
4.2. Ultrashort echo time (UTE) MRI agent has been approved by the united states food and
drug administration to date, tremendous effects have
100
Although conventional MRI pulse sequences have shown been made to develop targeted MRI probes for clinical and
CT-comparable detection of lung cancer, they are limited preclinical MRI. Their clinical translation could provide
to detecting signals from tissue or lesions with long T2 early detection, staging, prognosis, and insight into
and higher proton density, such as tumor mass. The complex biological activities.
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advancement of the UTE MRI pulse sequence has enabled
imaging of lung parenchyma along with its abnormalities Collagen type I is an extracellular matrix protein that
using an extremely short echo time to capture the is overexpressed and deposited during the progression of
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rapidly decaying T2 signal. 81,90-92 Meanwhile, UTE MRI is various diseases, including lung fibrosis and lung TME.
intrinsically insensitive to motion effect, that is, no gating The expression of collagen is also crucial in nodule
or breath-holding is required during UTE MRI scans. formation, cancer permeability, metastasis migration,
30,32-34
106-111
With recent upgrades in hardware and software, UTE and therapeutic responses. Caravan et al. and
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pulse sequences have been implemented in both clinical Ibhagui et al. have developed several probes to report
collagen bioactivity for the detection of lung fibrosis or
and preclinical settings over the past decade. 76,93-95 In recent fibrogenesis. The study of lung fibrosis is deeply related to
human studies, Ohno et al. 27,96 reported that the UTE pulse lung cancer, as they share common biological pathways
sequence was effective in detecting lung cancer nodules and biomarkers. Collagen-targeted MRI contrast agents
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as small as 4 mm, which is comparable to standard- or can also be applied to detect lung cancer, as lung TME
reduced-dose CT. Sanchez et al. performed T1W, T2W, overexpress collagen. 107,109
29
and UTE MRI on 36 patients and found that lung nodules
larger than 4 mm could be accurately detected. UTE MRI 5. Potential targeting biomarkers for early
has emerged as a promising alternative to conventional lung cancer detection
MRI pulse sequences for lung imaging, achieving
comparable imaging capability to CT without the need for Lung cancer is a heterogeneous disease at both the cellular
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radiation or breath-holding. 29,97 Moreover, it allows for the and histological levels. Identifying specific biomarkers
detection of lung tissue abnormalities such as fibrosis 98,99 according to the classification of lung cancer is crucial for
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and early-stage lung cancer nodules. better understanding its occurrence and development
and has significant implications for the early detection and
4.3. Contrast-enhanced molecular MRI treatment decisions.
About one-third of clinical MRI scans are administered In addition to type I collagen, several other collagen
with MRI contrast agents, as these agents provide types have been shown to be overexpressed in various
additional functional information. 100,101 Dynamic contrast- tumors, with increased collagen expression usually
enhanced (DCE) MRI involves the injection of MRI associated with tumor progression and poor prognosis.
contrast agents such as gadolinium-based contrast agents Type XI collagen α1 chain (COL11A1) is upregulated in
(GBCAs). GBCAs increase the contrast between healthy both lung adenocarcinoma and NSCLC and plays an
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and abnormal tissue by shortening the relaxation time of important role in the proliferation, migration, and invasion
water protons. Due to tumor angiogenesis and the richer of NSCLC, as well as in resistance to cisplatin. This
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vasculature of tumors compared to the lung parenchyma, indicates that COL11A1 is a promising biomarker for lung
extracellular fluid GBCAs enhance lung tumors during cancer. 117-121 The type VI collagen α6 gene (COL6A6), a
the blood pool phase. 100,101 Differences in vascularization tumor suppressor in NSCLC, can inhibit the tumorigenesis
patterns between different lung tumor subtypes enable DCE and progression of NSCLC by regulating the JAK signaling

Volume 2 Issue 3 (2024) 6 doi: 10.36922/arnm.4173