Immunotherapy response evaluation with (18)F-FDG-PET in patients with advanced stage renal cell carcinoma.

BACKGROUND: CT imaging is widely used for response evaluation of immunotherapy in patients with advanced stage renal cell carcinoma (RCC). However, this kind of treatment may not immediately be cytoreductive, although the treatment is successful. This poses new demands on imaging modalities. Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) proved to be useful in monitoring the effect of several antitumour treatments. We investigated the potential of FDG-PET for the evaluation of response to immunotherapy. METHODS: In seven patients with metastasized RCC, who were treated with either interferon-alpha (IFN-α) monotherapy or a combination of IFN-α, interleukin-2 and 5-fluorouracil, FDG-PET was performed prior and after 5 and 9 weeks of treatment. Quantitative changes of glucose metabolic rate (MRGlu) were compared with changes in tumour size on CT imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and to survival and progression-free survival. RESULTS: No consistent changes in MRGlu were observed within different response groups. And no correlation with CT imaging, neither with survival or progression-free survival, was found. CONCLUSION: In contrast to the positive results reported on (chemo) therapy response evaluation with FDG-PET in different malignancies, this imaging modality appears not useful in response monitoring of immunotherapeutic modalities in RCC.

(18)F-FLT-PET for Response Evaluation of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with Solid Tumors.

Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. This pilot study was used to explore if (18)F-fluoro-l-thymidine (FLT), a thymidine analogue positron emission tomography (PET) tracer and a surrogate marker for proliferation, can be used as an early predictor of response for patients with solid cancers treated with Selumetinib. FLT-PET scans were performed in four patients at baseline and after 2 weeks of treatment with Selumetinib. FLT uptake in tumors was analyzed qualitatively and quantitatively by measuring standard uptake value (SUV) max in regions of interest (ROI). Results were compared to computed tomography (CT) scans (baseline and after 8 weeks), which were evaluated using the response evaluation criteria in solid tumors (RECIST) 1.0 criteria. One patient with melanoma showed both a qualitative and quantitative decrease in FLT uptake associated with a decrease in sum of longest diameter of 12% RECIST on CT evaluation. Another patient who had colorectal carcinoma (CRC) showed a significant increase in FLT uptake with initially stable, but eventually progressive disease on CT. The other two patients (one with melanoma and one with CRC) showed no significant changes in FLT uptake, whereas CT evaluation showed progressive disease. This is the first report describing changes in FLT-PET in patients receiving Selumetinib. In two patients, changes in FLT uptake as early as after 2 weeks of treatment were consistent with CT results after 8 weeks. Biomarkers to predict and evaluate treatment the outcome of targeted therapies are highly warranted. These initial results need further investigation.

(18)F-fluoro-L-thymidine-PET for the evaluation of primary brain tumours in children: a report of three cases.

BACKGROUND: F-fluoro-L-thymidine (FLT) has been shown to be a useful PET tracer in the evaluation of brain tumours in adults. No studies of this modality in children with brain tumours, however, have been published. OBJECTIVE: In this report three children with brain tumours are presented in which FLT-PET was used for different diagnostic purposes, in addition to imaging with MRI and F-fluorodeoxyglucose-PET. The first patient showed that FLT-PET could be helpful in differentiating between infection and malignancy. In the second patient FLT-PET was used for differentiating recurrent disease from radiotherapy effects. In the third patient, in which biopsy was not possible, FLT-PET was used for the characterization of the tumour. CONCLUSION: These patients show that FLT-PET might be a useful modality in different stages of the evaluation of primary brain tumours in children. However, further research to determine the clinical value, relative to MRI and fluorodeoxyglucose-PET, is required before routine implementation of FLT-PET.

Increase in systemic blood pressure during intra-arterial PD123319 infusion: evidence for functional expression of angiotensin type 2 receptors in normal volunteers.

The functional existence of angiotensin type 2 (AT2) receptors in healthy humans is uncertain. A double-blind, randomized, crossover study was performed comparing forearm vascular responses to intrabrachial arterial PD123319 (a selective AT2 receptor antagonist, 10 microg/min) in healthy young, non-smoking volunteers following 1 week of telmisartan therapy (40-80 mg once daily) and 1 week of placebo therapy. No significant difference was found in baseline mean arterial pressure between telmisartan and placebo treatment. Baseline forearm blood flow (FBF) was significantly higher during telmisartan (2.69 +/- 1.28 ml/s) therapy than during placebo (1.86 +/- 0.75 ml/s). PD123319 did not alter FBF on either telmisartan or placebo therapy. However, significant increases in mean arterial pressure were observed during intra-brachial arterial infusions of PD123319 (p=0.003) during both placebo (80 +/- 9 to 92 +/- 17 mmHg) and telmisartan (80 +/- 11 to 90 +/- 14 mmHg) therapy suggesting the presence of functional AT2 receptors, possibly in locations other than the forearm resistance vessels. Intra-brachial arterial infusion of PD123319 (10 microg/min) has significant systemic effects, which appear more prominent than local changes in FBF and which are not influenced by angiotensin type 1 receptor blockade.

Haemodynamic and pulse wave responses to intravenous infusions of angiotensin II during chronic telmisartan therapy in normal volunteers.

INTRODUCTION: This study investigated the central haemodynamic, blood pressure (BP) and pulse wave responses to progressively increasing infusion rates of intravenous angiotensin II (Ang II) in normal volunteers during chronic therapy with telmisartan or placebo. MATERIALS AND METHODS: Ten normal volunteers, aged 21 33 years, completed a randomised, double-blind crossover study. Ang II was infused intravenously at increasing infusion rates (0 512 ng/minute) at the end of one week of telmisartan therapy (40 80 mg/day) and one week of placebo therapy. BP, central haemodynamics and pulse wave parameters were monitored continuously using a CardioDynamics Recorder, a Pulse Tracer Recorder and a Finipress Recorder. RESULTS: Baseline diastolic BP (57+12 vs. 67+13 mmHg) and pulse wave reflection index (RI) (38.4+18.6 vs. 60.6+12.5%) were significantly lower on telmisartan than on placebo therapy. Cardiac index (CI), systolic BP, systemic vascular resistance index (SVRI), RI and pulse wave stiffness index (SI) were all significantly increased in a dose-dependent manner by Ang II on placebo therapy. Telmisartan significantly (p<0.05) attenuated all of these responses to Ang II. Increases in BP during Ang II infusion were associated with increases in SVRI and CI. CONCLUSIONS: Telmisartan effectively blocked the effects of intravenous Ang II on CI, BP, RI and SI in healthy volunteers. Changes in CI make a major contribution to increase in BP response to intravenous Ang II in normal volunteers.