Monitoring Response to Radiotherapy in Human Squamous Cell Cancer Bearing Nude Mice: Comparison of 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG) and 3′-[18F]fluoro-3′-deoxythymidine (FLT)

Objective: The uptake of 3′-[18F]fluoro-3′- deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG). Materials and Methods: Nude mice bearing established human head and neck xenografts (HNX-OE; nu/nu mice) were locally irradiated (three fractions/week; 22 Gy) using a 150-kVp unit. Multiple FDG- and FLT-PET scans were acquired during treatment. Tumor volume was determined regularly, and tissue was analyzed for biomarkers involved in tracer uptake. Results: Both groups revealed a significant decline in tumor volume (P∈<∈0.01) compared to untreated tumors. For FDG as well as for FLT, a significant decline in retention was observed at day 4. For FLT, most significant decline in retention was observed at day 12; whereas, for FDG, this was already noted at day 4. Maximum decline in tumor-to-nontumor ratios (T/NT) for FDG and FLT was 42∈±∈18% and 49∈±∈16% (mean∈± ∈SD), respectively. FLT uptake was higher then that of FDG. For FLT, statistical significant correlations were found for both tumor volume at baseline and at day 29 with T/NT and ΔT/NT. All tumors demonstrated expression of glucose transporter-1, thymidine kinase-1, and hexokinase II. No differences were found for amount of tumor cells and necrosis at the end of treatment. Conclusion: This new experimental in vivo model supports the promise of using FLT-PET, as with FDG-PET, to monitor response to external radiotherapy. This warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy

Experimental and Clinical Analysis of the Characteristics of a Chimeric Monoclonal Antibody, M0v18, Reactive with an Ovarian Cancer-AssociatedAntigen

Monoclonal antibody (Mab) MOvi 8 preferentially reacts with gynecolo @ carcinomas.We haveanalyzedthe character istics of munne MOvi 8 (m-MOvl 8) and chimeric MOvi 8 (c MOvi 8). We found no differences in affinity and binding to IGROV1cellsbetweenc-MOvl 8 a

The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis

Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA). Notably, positive correlations have been reported between synovial macrophage infiltration and disease activity as well as therapy outcome in RA patients. Hence, macrophages can serve as an important target for both imaging disease activity and drug delivery in RA. Folate receptor β (FRβ) is a glycosylphosphatidyl (GPI)-anchored plasma membrane protein being expressed on myeloid cells and activated macrophages. FRβ harbors a nanomolar binding affinity for folic acid allowing this receptor to be exploited for RA disease imaging (e.g., folate-conjugated PET tracers) and therapeutic targeting (e.g., folate antagonists and folate-conjugated drugs). This review provides an overview of these emerging applications in RA by summarizing and discussing properties of FRβ, expression of FRβ in relation to macrophage polarization, FRβ-targeted in vivo imaging modalities, and FRβ-directed drug targeting

A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model

<div><p>Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of <i>in vivo</i> visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.</p></div

Clarifying the diagnosis of clinically suspected recurrence of cervical cancer: impact of 18F-FDG PET

Clarifying the diagnosis of clinically suspected recurrence of cervical cancer can be challenging. The aim of this study was to investigate the clinical value of (18)F-FDG PET in this context. The medical records of a cohort of 40 (18)F-FDG PET referrals in whom recurrence of cervical cancer was clinically suspected were reviewed. Two expert gynecologic oncologists assessed the level of pre-PET clinical doubt, quality of pre-PET work-up, and impact of (18)F-FDG PET on diagnostic understanding and management using questionnaires. In patients with clinically equivocal recurrence, (18)F-FDG PET had a sensitivity of 92% and a specificity of 93% (prevalence, 65%). Before (18)F-FDG PET, there was high disagreement about the adequacy of the conventional work-up (intraclass correlation coefficient [ICC], 0.25) and the presence of recurrence (ICC, 0.24). (18)F-FDG PET increased experts' confidence (median increase, 14% and 25%; P < 0.0001) and diagnostic agreement (from 68% to 98%; ICC, from 0.24 to 0.95). When (18)F-FDG PET was positive for recurrence, the median overall survival was 13 mo. For patients with negative (18)F-FDG PET findings, the median survival was not reached (log rank, 15.50, P = 0.0001). When the treatment plan was categorized as local therapy, systemic therapy, and expectative management, (18)F-FDG PET changed the treatment plan in half of all cases. The 2 experts reported that (18)F-FDG PET led to a better diagnosis and a beneficial change in management in, respectively, 60% and 65% of cases. (18)F-FDG PET can help to clarify the diagnosis of clinically suspected recurrence of cervical cancer. In this patient population, (18)F-FDG PET had significant value in diagnostic understanding and management of recurrent cervical cancer, facilitating decision making and treatment planning. Therefore, (18)F-FDG PET should be part of the diagnostic work-up in detection of recurrent cervical cancer. The high positive predictive value of (18)F-FDG PET in these patients suggests that inclusion in intervention trials might be based on a positive (18)F-FDG PET sca

Longitudinal multimodal imaging assessment of <i>in vivo</i> bladder tumor growth.

<p>(A) BLI acquisition of MB49-luc tumor-bearing C57Bl/6 mice during local injury method 18 minutes after s.c. luciferin injection. BLI is expressed as the number of photons/sec; the graph is representing the increase in bioluminescence activity over time (n = 4, mean ± SD). (B) HRUS results expressed as tumor volume in mm³ over time after tumor cell implantation (n = 4, mean ± SD). (C) Serial PAI measurements showing average sO₂ values in tumor bearing mice (n = 4, mean ± SD).</p

Comparison of BLI, HRUS and PAI images with macroscopic analysis of tumor volumes.

<p>(A) BLI image, (B) longitudinal section of the bladder of HRUS image, (C) PAI image and (D) <i>ex vivo</i> bladder on sacrificing day for comparison of multimodal images and macroscopic analysis of tumor volumes.</p

Histopathology and immunohistochemistry.

<p>(A) HE images confirm imaging results and show tumor growth extending from the bladder wall in to the bladder lumen. Tumor bearing mice show (B) positive Ki-67 staining, (C) positive PECAM staining as well as (D) high TRAIL expression.</p

Example of HRUS image.

<p>HRUS is able to provide specific anatomical information of bladder tumor development in a 3-dimensional plane. The tumor size was assessed based on the ROIs drawn around the tumor borders for every slice of 125 μm. Tumor is marked in blue.</p

Visualization of the scratching procedure with HRUS.

<p>HRUS images were obtained during the optimized local injury method in a sham mouse. Marked in blue and red is the scratching blunted needle and the bladder wall, respectively. (A) scratching of the bladder wall for 1 minute, (B) bladder immediately after the procedure, (C) bladder region after 10 days.</p