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Companion diagnostic (CDx) tests play important roles in identifying oncogenic driver genes and tailoring effective molecularly targeted therapies for lung cancer patients. In Japan, the Oncomine Dx target test (ODxTT) and the AmoyDx pan lung cancer PCR panel (AmoyDx) are prominent CDx tests and only one of these tests is covered by the domestic insurance system. However, these CDx tests cover different target regions and apply different technologies (ODxTT is amplicon-based next-generation sequencing and AmoyDx is multiplex PCR-based assay), which may lead to missing of actionable mutations affecting patient prognosis. Here, we performed a direct comparison analysis of 1059 genetic alterations of eight driver genes from 131 samples and evaluated the concordance between two CDx tests for detecting actionable variants and fusions. When excluding the eight uncovered variants (ODxTT: two variants, AmoyDx: six variants), the overall percent agreement was 97.6% (1026/1051) with 89.0% of overall positive percent agreement (89/100) and 98.5% of overall negative percent agreement (937/951). Of the 25 discordant genetic alterations, two were undetected despite being covered in the AmoyDx (one EGFR variant and one ROS1 fusion). Furthermore, there were potential false positives in the ODxTT (nine MET exon 14 skippings) and in the AmoyDx (five variants, six ROS1 and three RET fusions). These potential false positives in the AmoyDx likely due to non-specific amplification, which was validated by the unique molecular barcoding sequencing. The ODxTT missed two uncovered EGFR rare variants, which was visually confirmed in the raw sequencing data. Our study provides insights into real-world performance of CDx tests for lung cancer and ensures reliability to advance precision medicine., (© 2024. The Author(s).)

Lung cancer is a leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor (EGFR) driver mutations are crucial for treatment decisions for patients with non-small cell lung cancer (NSCLC). This study aimed to assess the differences in EGFR mutation detection between two companion diagnostic (CDx) tests-the Oncomine Dx Target Test (ODxTT) and the AmoyDx Pan Lung Cancer PCR Panel-and their impact on treatment applicability. To this end, we used an in-house targeted sequencing dataset of 282 samples from 127 EGFR-mutated NSCLC patients to simulate the concordance between the EGFR variants targeted by the ODxTT and AmoyDx panel, the oncogenicity of the variants, and their therapeutic potential. Of the 216 EGFR mutations identified by the in-house panel, 51% were detectable by both CDx tests, 3% were specific to ODxTT, and 46% were not targeted by either test. Most non-targeted mutations did not have oncogenicity and were located outside exons 18-21. Notably, 95% of the mutations detectable by both tests had potential oncogenicity. Furthermore, among the 96 patients harboring actionable EGFR mutations, 97% had mutations detectable by both CDx tests and 1% by ODxTT, while 2% had mutations not covered by either test. These findings suggest that while both CDx tests are effective in detecting almost all actionable EGFR mutations, ODxTT provides slightly broader coverage. These results emphasize the importance of selecting appropriate CDx tests to inform treatment decisions for EGFR-positive NSCLC patients., (© 2024. The Author(s).)

In this study, we investigated the association between PD-L1 expression in tumor cells and underlying genetic mutations, which was analyzed in detail using laser microdissection and next-generation sequencing analysis. To investigate whether driver mutations are involved in the background of PD-L1 expression, the EGFR major activating mutation was selected as the most frequent driver mutation. Surgical resection specimens were used to extract sufficient amounts of nucleic acids for analysis, and the high tumor proportion score (TPS:100%) and low (TPS: 0%) PD-L1-expressing parts of the tumor were each laser microdissected to examine the association between PD-L1 expression heterogeneity and genetic mutations within the same tumor. The association between PD-L1 heterogeneity and gene mutations within the same tumor was investigated. Analysis showed no association between PD-L1 expression heterogeneity and genetic variants, which were found to be almost identical. However, PD-L1 expression was found to be associated with the number of tumor infiltrating lymphocytes (TILs) present in the tumor, which may be related to whether or not lymphocytes can infiltrate into the tumor depending on the tumor histological type (solid pattern, lepidic pattern, etc.) and other factors., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background and Objective: The Oncomine Dx Target Test (ODxTT) has been used as a companion diagnostic test for lung cancer. Here, we evaluated whether the amount of nucleic acid and the degree of RNA degradation are related to the success of the ODxTT., Methods: This study included 223 samples from 218 patients with lung cancer. For all samples, DNA and RNA concentrations were quantified using Qubit, and the degree of RNA degradation was evaluated using the Bioanalyzer., Results: Of the 223 samples, 219 samples were successfully analyzed in the ODxTT and four were not. DNA analysis failed in two samples, which were attributed to low DNA concentrations and both were cytology specimens. Meanwhile, RNA analysis failed in the other two samples. These samples had sufficient amounts of RNA, but it was highly degraded with DV200 (the percentage of RNA fragments > 200 base pairs) less than 30. Compared with RNA samples with DV200 ≥ 30, analysis of RNA with DV200 < 30 yielded significantly fewer reads for the internal control genes. This test showed actionable mutations were identified in 38% (83/218) of all patients and in 46.6% (76/163) of patients with lung adenocarcinoma., Conclusions: DNA concentration and degree of RNA degradation are key factors determining the success of diagnostic testing by the ODxTT., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Genomic profiling in lung cancer is essential for precision medicine. Cytological specimens provide an alternative to formalin-fixed paraffin-embedded (FFPE) samples for comprehensive genomic analysis. However, this approach remains challenging when a limited number of tumor cells are available. We applied whole genome amplification (WGA) to cytology specimens to overcome this limitation., Methods: Using a lung cancer panel targeting 58 genes, we performed next-generation sequencing of whole genome-amplified DNA extracted from cytological specimens containing 10-20 tumor cells (cyto-WGA) and DNA from corresponding FFPE tumor tissue. We compared sequencing data from cyto-WGA and FFPE samples to examine the detection accuracy of copy number variations and oncogenic and drug-matched variants., Results: The DNA quality and quantity from cyto-WGA were higher than those from FFPE samples (p < .0005 and p < .05, respectively). Sequencing metrics of cyto-WGA and FFPE tissues showed no difference in the number of mapped reads and mean coverage depth, but there were significant differences in the on-target rate (p < .05) and uniformity (p < .0005). Copy number variations in cyto-WGA samples (n = 211) were higher than in FFPE samples (n = 9) (p < .0001). Fourty nine oncogenic variants were detected in cyto-WGA and 39 in FFPE. Of these variants, 34 (63%) were present in both samples. In addition, all 16 drug-matched variants were detected in FFPE and cyto-WGA samples with 100% concordance., Conclusion: Cyto-WGA can be a feasible and alternative method to detect oncogenic and drug-matched variants., (© 2022 American Cancer Society.)

Background: Molecular testing is critical for identifying actionable variants in lung cancer for precision medicine. When tumor tissue samples are unavailable, archived cytological specimens (ACSs) can be used. The authors examined whether oncogenic variants could be accurately detected in ACSs versus paired formalin-fixed, paraffin-embedded (FFPE) tumor tissues with in vitro diagnostic tests., Methods: The authors collected 18 ACSs and 15 FFPE tissues from 15 patients with lung cancer and investigated genomic profiles with the Oncomine Dx Target Test Multi-CDx system, which is an integrated next-generation sequencing platform that comprehensively examines 4 companion diagnostic target genes (epidermal growth factor receptor [EGFR]; B-Raf proto-oncogene, serine/threonine kinase [BRAF]; anaplastic lymphoma kinase [ALK]; and ROS proto-oncogene 1, receptor tyrosine kinase [ROS1]). They compared the quantity and quality of extracted nucleic acids, the sequencing quality control (QC), and the detected variants between ACSs and FFPE tissues., Results: The total amount of DNA and RNA obtained from 1 slide was higher in FFPE tissues than ACSs. The RNA integrity number was higher in ACSs. There were no differences in sequencing QC between ACSs and FFPE tissues. A total of 21 variants, including EGFR mutations and ALK and ROS1 fusion genes, were detected in both ACSs and FFPE tissues with 100% concordance., Conclusions: ACSs can be a feasible alternative with which to identify actionable mutations and fusion genes via the Oncomine Dx Target Test Multi-CDx system., (© 2021 American Cancer Society.)

Objectives: Intratumor heterogeneity (ITH) is reportedly involved in the clinical course and in the response to treatment, although the detailed mechanism underlying this effect remains unclear. In this study, we investigated the effect of epithelial growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment on ITH with an EGFR-mutated lung cancer patient using the multiregional sequence (MRS) analysis of surgical specimens both before and after EGFR-TKI treatment., Materials and Methods: We performed the MRS analysis of primary lung and resistant metastatic lesions, respectively through targeted sequencing, covering whole exons of 53 significantly mutated, lung cancer-associated genes. Through the comparison of primary lung and metastatic lesion mutation profiles, along with PyClone analysis of sequence data, we revealed the trajectory of resistant clones from a primary to metastatic site., Results: MRS revealed high ITH at the primary lung lesion and low ITH at the metastatic site, suggesting that the EGFR-TKI treatment followed an attenuated progression pattern. Tumor cell clones harboring EGFR G719S, L861R, SMARCA4 R1192C and KMT2D Q1139R mutations in the primary lesion metastasized and acquired the EGFR-TKI-resistant EGFR C797S mutation., Conclusion: MRS revealed attenuated progression pattern and clonal evolution. In the case of high ITH with attenuated progression pattern, as observed in the present case, local treatment may be effective when oligometastasis emerged., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introductions: When tumor tissue samples are unavailable to search for actionable driver mutations, archival cytology samples can be useful. We investigate whether archival cytology samples can yield reliable genomic information compared to corresponding formalin-fixed paraffin-embedded (FFPE) tumor samples., Patients and Methods: Pretreatment class V archival cytology samples with adequate tumor cells were selected from 172 lung cancer patients. The genomic profiles of the primary lung tumors have been analyzed through whole-exome regions of 53 genes. We compared the genomic profiles based on the oncogenicity and variant allele frequency (VAF) between the archival cytology and the corresponding primary tumors. We also analyzed the genomic profiles of serial cytological samples during the treatment of EGFR-TKI., Results: A total of 43 patients were analyzed with the paired samples for DNA mutations and other three patients were analyzed for their fusion genes. A total of 672 mutations were detected. Of those, 106 mutations (15.8%) were shared with both samples. Sixty of seventy-seven (77.9%) shared mutations were oncogenic or likely oncogenic mutations with VAF ≧10%. As high as 90% (9/10) actionable driver mutations and ALK and ROS1 fusion genes were successfully detected from archival cytology samples. Sequential analysis revealed the dynamic changes in EGFR-TKI-resistant mutation (EGFR p.T790M) during the course of treatment., Conclusion: Archival cytology sample with adequate tumor cells can yield genetic information compared to the primary tumors. If tumor tissue samples are unavailable, we can use archival cytology samples to search for actionable driver mutations., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Conventional next generation sequencing analysis has provided important insights into cancer genetics. However, the detection of rare (low allele fraction) variants remains difficult because of the error-prone nucleotide changes derived from sequencing/PCR errors. To eliminate the false-positive variants and detect genuine rare variants, sequencing technology combined with molecular barcodes will be useful. Here, we used the newly developed dual-molecular barcode technology (Ion AmpliSeq HD) to analyze somatic mutations in 24 samples (12 tumor tissues and 12 plasma) from 12 patients with biliary-pancreatic and non-small cell lung cancers. We compared the results between next generation sequencing analysis with or without molecular barcode technologies. The variant allele fraction (VAF) between non-molecular barcode and molecular barcode sequencing was correlated in plasma DNA (R 2  = 0.956) and tumor (R 2  = 0.935). Both methods successfully detected high VAF mutations, however, rare variants were only identified by molecular barcode sequencing and not by non-molecular barcode sequencing. Some of these rare variants in tumors were annotated as pathogenic, and therefore subclonal driver mutations could be observed. Furthermore, the very low VAF down to 0.17% were identified in cell free DNA in plasma. These results demonstrate that the dual molecular barcode sequencing technologies can sensitively detect rare somatic mutations, and will be important in the investigation of the clonal and subclonal architectures of tumor heterogeneity.

Introduction: Next-generation sequencing (NGS) of multiple metastases in an advanced cancer patient reveals the evolutional history of the tumor. The evolutionary model is clinically valuable because it reflects the future course of the tumorigenic process and prognosis of the patient., Materials and Methods: We experienced two lung cancer patients whose clinical courses were abruptly deteriorating resulting in very poor prognosis. To investigate the evolutionary model of these patients, we performed targeted sequencing covering whole exons of 53 significantly mutated genes associated with lung cancer of multiple metastases by autopsy. We conducted PyClone analysis to infer subclonal archtecture of multi-lesional samples., Results: The NGS analysis revealed both patients harboring multiple clonal driver mutations. In Case.1, KRAS Q61H, KEAP1 G333C, STK11 K312*, RBM10 Q320* and MGA I1429V and in Case.2, TP53 R337L, TP53 Q192*, PTEN W274C, RB1 P29fs and CREBBP P696L with high allele fraction were detected in all lesions. These mutations were clustered and occupied major population across multi-lesional tumor samples. Our data suggested their lung cancers progressed with punctuated and big bang evolutional model., Conclusion: We should pay attention to clinical course of lung cancer patients harboring multiple clonal driver mutations in their primary lesions. Their punctuated and big bang evolutionary process could develop systemic clinically undetectable metastases with an unexpected speed., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose concerning the study., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non-small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown., Methods: This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome., Results: Of the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When "2 weeks" was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response., Conclusions: In patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

Background: Sarcomatoid cancer is defined by the World Health Organization as a category of non-small cell lung cancers with sarcoma or sarcoma-like differentiation. They are characterized by poor prognosis and resistance to conventional chemotherapy. However, the mutational profile of sarcomatoid cancer remains yet to be elucidated. Sarcomatoid cancers are usually biphasic tumors composed of carcinomatous and sarcomatous components, but the evolutional development of sarcomatoid cancer is controversial., Case Presentation: We present an illustrative case of sarcomatoid cancer composed of three different histological areas. Targeted sequencing of 53 lung cancer-related genes was performed in each component and their phenotypic changes were correlated with stepwise addition of genetic changes., Conclusion: Sarcomatous change of carcinoma occurs in the case of sarcomatoid cancer, and phenotypic changes to sarcomatoid cancer are associated with the addition of mutation patterns and derived from poorly differentiation tumor.

BACKGROUND The analysis of circulating tumor DNA (ctDNA) is expected to be a modality to determine the status of cancer in real time. This case indicated utilities and issues in measuring the ctDNA in cancer patients. CASE REPORT A 45-year-old woman with metastatic breast cancer was treated with bevacizumab and paclitaxel. The lung metastases were decreased but the meningitis carcinoma developed rapidly and she died. During the treatment with bevacizumab and paclitaxel, blood samples were taken serially and ctDNA was analyzed using a next-generation sequencer. TP53 frameshift mutation (TP53; p.Arg158fs with 7 nucleotides deletion) was identified in the tumor, and dynamic change in this mutation in ctDNA was observed in serially sampled plasma in this patient. We observed a rapid decrease of TP53 mutation at the beginning of treatment, then it increased as a sign of relapse. However, the high allelic fraction value of TP53 mutation was not consistent during the progression of cancer, suggesting that several factors affected the value of ctDNA. CONCLUSIONS Although this is a single-case experience, it strongly suggests ctDNA could be a modality to determine the cancer status in real time. However, we found that several factors affected the value of ctDNA. Further investigations are needed to reveal the significance of these very high-sensitivity changes., Competing Interests: Conflicts of Interest: None declared Disclosure statement The authors have no conflict of interest to declare.

Liquid biopsies such as circulating tumor DNA in plasma and disseminated tumor cells in the bone marrow are currently available. However, it is unclear which types of samples are appropriate for detecting tumor DNA in these biopsies. Here, we collected primary tumors, pulmonary venous blood, peripheral blood, and rib bone marrow fluid from 10 lung cancer patients. Targeted deep sequencing was performed to identify mutations across 70 specimens. As a result, a total of 43 mutations were identified in the primary tumors. The mutation in the tumors was also identified in circulating tumor DNA in the pulmonary venous and peripheral blood in two patients. These patients showed poor prognosis, as compared to the other patients. However, no mutation was identified in the bone marrow in any of the patients. These results demonstrated that circulating tumor DNA in plasma is more sensitive and clinically useful as a biomarker as compared to DNA in bone marrow fluid.

A micropapillary pattern is defined as papillary tufts without a fibrovascular core and is known to be a factor that indicates a poor prognosis in numerous cancers. However, their role in lung adenocarcinoma has not been investigated widely. In 185 cases of small-size lung adenocarcinoma (< or =3 cm), cases with a micropapillary pattern ratio of more than 1% (analyzed by NIH image) were defined as micropapillary pattern positive. Correlations between the micropapillary pattern and clinicopathological factors were investigated and immunohistochemical expression of mucin and various antigens was examined in regions with and without micropapillary patterns. Micropapillary pattern-positive tumors (micropapillary pattern ratio > or =1%) were observed in 11.4% of cases (21/185) and the micropapillary pattern ratio correlated with TNM stage (P=0.0002), lymphatic invasion (P=0.0002) and lymph node metastasis (P=0.03). Disease-free interval (P<0.0002) and survival (P=0.027) were significantly shorter for micropapillary pattern-positive patients, and micropapillary pattern-positive stage IA cases also had a significantly shorter disease-free interval (P<0.0001). MUC1 was expressed strongly across the surface of the micropapillary structure, whereas MUC4 tended to show lower expression in the micropapillary pattern. It was noteworthy that the disease-free interval in patients with high surfactant apoprotein A expression was significantly better than in patients with low surfactant apoprotein A expression (P=0.03), and no recurrence or death occurred in patients with high surfactant apoprotein A expression. Our results show that the micropapillary pattern ratio correlates with lymphatic invasion and lymph node metastasis, and that a high micropapillary pattern ratio leads to a poor prognosis. High MUC1 expression on the surface is an important characteristic of a micropapillary pattern, and reduced surfactant apoprotein A expression in the micropapillary pattern may be an excellent indicator for poor prognosis in small-size lung adenocarcinoma.

The mortality of lung cancer remains high, despite improved diagnostic techniques that allow small lung tumors to be detected. In this study, we evaluated the prognostic significance of the tracheal mucin MUC4 by immunohistochemical investigation of the expression profiles of MUC4, ErbB2, p27 and MUC1 in lung adenocarcinoma specimens (non-bronchiolo-alveolar type, < or =3cm) from 185 patients. MUC4 is a membrane mucin, similarly to MUC1, and in addition MUC4 functions as an intra-membrane ligand for receptor tyrosine kinase ErbB2 and is associated with regulation of p27. However, MUC4 expression was found to be unrelated to expression of MUC1, ErbB2 and p27 in small-sized lung adenocarcinomas. The disease-free interval (DFI) and survival rate of 25 patients with high MUC4 expression (> or =25% of neoplastic cells stained) were significantly lower than those of 160 patients with low MUC4 expression (<25% of neoplastic cells stained) (P<0.05), whereas ErbB2 and p27 expression showed no significant correlation with DFI and survival. Univariate analysis showed that high MUC4 and p27 expression correlated with blood vessel invasion (P=0.0004), and MUC4 expression was frequently detected in regions of stromal invasion. In addition, the survival rate of stage IA patients with high MUC4 expression was significantly lower than that of stage IA patients with low MUC4 expression (P<0.05). In conclusion, high MUC4 expression in small-sized lung adenocarcinomas correlates with a short DFI and a poor survival rate. Therefore, MUC4 expression might be a new independent factor for prediction of outcome and indication of poor prognosis in lung adenocarcinoma.

Aim: Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Here, we aim to report a unique method to predict the recurrence and outcome of patients with pulmonary adenocarcinomas., Methods and Results: Immunohistochemical expression of MUC1 mucin and surfactant apoprotein A (SP-A) was examined in 185 cases of surgically removed lung adenocarcinomas of non-bronchioloalveolar type smaller than 30 mm. Staining results were evaluated semiquantitatively, and the expression of MUC1 and SP-A was compared in each case. There were 140/185 (76%) cases showing MUC1 expression higher than SP-A expression (MUC1>SP-A), and 45/185 (24%) cases showing MUC1 expression lower than or equal to SP-A expression (MUC1SP-A pattern, but in 7% (3/45) of the patients with a MUC1< or =SP-A pattern after the median observation period of 41 months (1-99 months) (P < 0.01). The MUC1>SP-A group showed higher recurrence and worse survival than the MUC1

A 44-year-old woman was admitted to our hospital for evaluation of an abnormal lung shadow. Chest computed tomography (CT) revealed a tumor surrounded by air-space and an infiltrative shadow in the right S2. Right upper lobectomy was performed and pulmonary sclerosing hemangioma was diagnosed. Usually, pulmonary sclerosing hemangioma shows a solitary round nodule on a chest CT scan. We report a case of pulmonary sclerosing hemangioma with an unusual shadow on a chest CT scan, and review the literature.

Serial lung images with N-isopropyl-p-[I-123]-iodoamphetamine (I-123 IMP) were obtained to assess the imaging findings and to clarify the lesion to uptake relationships in 74 lesions in 73 patients with various histological types of bronchogenic carcinoma. A decreased uptake area was observed in all 74 lesions in the initial one or two-min I-123 IMP image. The initial image was analogous to a Tc-99m MAA lung perfusion image in 70 patients in whom both lung imaging procedures were performed. The imaging findings changed following this initial phase. At 4 hr, the lesion was depicted as either areas of decreased uptake or increased uptake or a combination of the two. Comparison between the lesion findings in the 4-hr I-123 IMP images, radiograms and removed specimens revealed that areas of decreased uptake corresponded to the cancerous portions of the lung mass or pleural effusion and areas of increased uptake corresponded to inflammatory portions including obstructive pneumonitis and/or collapse. Thus, the 4-hr I-123 IMP lung images can be used to discriminate the cancerous portion from associated secondary changes, obstructive pneumonitis and/or collapse.

In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.