Abstract Development of novel methods of early diagnosis of lung cancer is one of the major tasks of contemporary clinical and experimental oncology. In this study, we utilized the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice as an animal model for development of a new imaging technique for early diagnosis of lung cancer. Lung cancer cells in A/J mice overexpress nicotinic acetylcholine receptors. Longitudinal CT scans were carried out over a period of 8 months after NNK treatment, followed by PET/CT scans with ¹⁸F-Nifene that binds to α4-made nicotinic receptors with high affinity. PET/CT scans of lungs were also obtained ex vivo. CT revealed the presence of lung nodules in 8-month NNK-treated mice, while control mice had no tumors. Imaging of live animals prior to necropsy allowed correlation of results of tumor load via PET/CT and histopathological findings. Significant amount of 18F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of ¹⁸F-Nifene. Quantitative analysis of the extent and amount of ¹⁸F-Nifene binding in lung in vivo and ex vivo demonstrated a higher tumor/nontumor ratio due to selective labeling of tumor nodules expressing abundant α4 nicotinic receptor subunits. For comparison, we performed PET/CT studies with ¹⁸F-FDG, which is used for the imaging diagnosis of lung cancer. The tumor/nontumor ratios for ¹⁸F-FDG were lower than for ¹⁸F-Nifene. Thus, we have developed a novel diagnostic imaging approach to early diagnosis of lung cancer using ¹⁸F-Nifene PET/CT. This technique allows quantitative assessment of lung tumors in live mice, which is critical for establishing tumor size and location, and also has salient clinical implications.
Keywords: F-Nifene; ¹⁸F-FDG; PET/CT imaging; nicotinic receptors; NNK; A/J mice; lung cancer

Abstract This report describes a case of a patient who developed therapy-related acute myeloid leukemia five years after initiating chemotherapy for follicular lymphoma. The patient had been treated with multiple chemotherapeutic regimens, including anthracycline and etoposide (VP-16), as well as with radiation therapy for refractory follicular lymphoma over the preceding five years. The patient subsequently developed myelodysplastic syndrome (MDS) with karyotypic abnormalities of monosomy 7 and del (q11; q13.3) followed by acute myeloid leukemia (AML) with an additional balanced translocation of t(9;22)(q34;q11) and t(3;21)(q26;q22). Reverse transcription-polymerase chain reaction amplification of the patient’s RNA showed a fusion transcript of minor BCR-ABL but not EVI1-RUNX1 (AML1) genes. Imatinib therapy resulted in regression of AML, but the patient soon became refractory to chemotherapy and died. Therapy-related acute leukemia develops mostly as non-lymphoid leukemia with unbalanced aberrations of monosomy 7 and 5 or balanced aberrations involving 11q23 and 21q22, but Philadelphia chromosome is uncommon. In addition, simultaneous occurrence of both t(9;22)(q34;q11) and t(3;21)(q26;q22) balanced aberrations in t-MDS/t-AML is a very rare event. The balanced translocations detected in this case suggest another mechanism by which t-AML can develop after chemotherapy and radiation therapy for follicular lymphoma.
Keywords: therapy-related myelodysplastic syndrome (t-MDS); therapy-related acute myeloid leukemia (t-AML); t(9;22); t(3;21); Philadelphia chromosome; follicular lymphoma; imatinib; chemotherapy