Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors.

BACKGROUND: To evaluate the role of FDG-PET in assessing anti-tumor efficacy of molecular targeted drugs, we prospectively performed FDG-PET and CT for response evaluation in patients treated with lapatinib, a dual inhibitor of ErbB1 and ErbB2 tyrosine kinases. METHODS: Lapatinib was given orally once a day at doses ranging from 1200 to 1800 mg in a phase I study. CT and FDG-PET were performed before treatment, and at 1, 2 and 3 months after the initiation of the treatment and every 2 months thereafter. RESULTS: A total of 29 FDG-PET examinations were performed in eight patients with various solid tumors and the metabolic activity in the tumor was evaluated as SUVmax. The best responses, as assessed by CT, were as follows; one partial response, four stable disease and three disease progression. The partial response was observed in a patient with trastuzumab-resistant breast cancer, whose SUVmax was decreased by 60% from baseline. In all of the four patients whose best response was stable disease, the SUVmax was decreased by 6-42% one month after the start of treatment. Prolonged stable disease (10 months) was observed in a patient with colon cancer, whose SUVmax was decreased by 42%. In the patient group with disease progression, SUVmax was increased in two out of three patients. CONCLUSIONS: FDG-PET detected decreases in the metabolic activity of the tumors in patients who experienced clinical benefits on treatment with lapatinib. Thus, FDG-PET may be useful for the evaluation of molecular targeted drugs, such as lapatinib.

Proposal of blood volume-corrected model for quantification of regional cerebral blood flow with H2 15O-PET and its application to AVF.

PURPOSE: It is generally assumed that vascular tracer activity is negligible in the quantification of regional cerebral blood flow (rCBF) with H2 15O and positron emission tomography (PET) under normal conditions. We attempted to surpass the assumption of abnormal vascular conditions where the vascular tracer activity is significant by introducing the vascular component into the model. MATERIALS AND METHODS: H2 15O-dynamic and C15O PET scans were performed in an arteriovenous fistula (AVF) patient. Time-activity curves of regions of interest (ROIs) were analyzed with nonlinear least-square approximation to estimate the rCBF and fractional arterial blood volume (v(a)) simultaneously with the proposed model and the standard model. RESULTS: The proposed model curve showed a fit to the time-activity curve of H2 15O at an ROI containing an enlarged vascular space induced by the AVF. The relation between the estimated v(a) and CBV obtained with C15O-PET revealed that the ratio of v(a) to CBV was approximately 0.23. The estimated rCBF with the proposed model in nonlesion ROIs corresponded to those of the standard model, with the estimated V(d) 0.94 ml/ml. CONCLUSION: The results supported the hypothesis that the blood volume-corrected model is applicable to the quantification of rCBF in a region with abnormal vascular structure. Furthermore, one of the advantages of the model is the feasibility of simultaneous estimation of the rCBF and arterial blood volume with dynamic-H2 15O PET scans.

Nuclear medical PET-study in the causal relationship between mastication and brain function in human evolutionary and developmental processes.

The principal author (Kubote 1995, 1997, 1998, 1999, 2000 a, b) has proposed that chewing food well from infancy will lead to a clear-headed and robust person, following which the same concept has been presented to the general public by the mass media. Unfortunately, however, there does not yet seem to be any direct evidence to support this claim. It is thus necessary to review mastication from the standpoint of the new concept of evidence-based medicine (EBM) and to create a new direction in medicodental research and treatment from the viewpoint of human evolution, because the causal relationship between mastication and brain function has never been clarified either in fossil science research or in the modem scientific bibliography. To confirm the human historical fossil record in regard to the causal relationship between the development of mastication and brain function in human evolutionary processes, the effect of gum chewing on brain reaction was examined in humans by means of a positron-emission tomography (PET) camera (Momose et al. 1997) after an antecubital intravenous injection of H215O. Powerful activation of the cortical cells was demonstrated in multiple cortical areas involving the marginal areas of the bilateral central sulci of the cerebral cortex (Fig. 1), and the activated areas coincided with our previous results in region of interest (ROI) analysis (Momose et al. 1887). Three-dimensionally, numerous cortical cells were shown to form nuclei on relief maps (Fig. 2). As diets and feeding habits changed in a stepwise manner from frugivorous to omnivorous via herbivorous and carnivorous over the lengthy progress of evolution, the brain concomitantly grew and the cranial capacity gradually increased in volume from 500 cm3, food from plant sources to animal sources (700 cm3), and then to both (1500 cm3), during the human evolutionary and developmental processes. Gradual increases in the cranial capacity of human fossils during the developmental stage have been demonstrated also by PET images of the human brain acquired by means of a PET camera and an antecubital intravenous injection of H215O during mastication that showed powerful activation of cortical cells in multiple areas. It could be concluded that human fossils give us concrete information on how to feed our children in the modern human life style from infancy to adulthood, so that we should bring children up by adhering to images of the principal feeding habits discovered during this research on human evolutionary and developmental processes.