Prognostic value of [<Superscript>18</Superscript>F]FDG-PET/CT in multiple myeloma patients before and after allogeneic hematopoietic cell transplantation

Purpose

Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using ¹⁸F-2’-deoxy-2’-fluorodeoxyglucose ([¹⁸F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

In this retrospective analysis, we evaluated [¹⁸F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUV_max) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed.

Results

PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p?<?0.001, post-HCT p?<?0.005). High FDG-uptake (SUV_max?>?6.5) revealed a significantly shortened survival compared to patients with a lower SUV_max (<6.5) (OS, 5.0?±?1.1 m vs. not reached - longest 122.0 m; p?<?0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p?<?0.001; post-HCT PFS: p?<?0.001, OS: p?=?0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [¹⁸F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone.

Conclusion

[¹⁸F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.

     

A randomized controlled trial of manual therapy and pneumatic compression for recovery from prolonged running – an extended study

Manual therapy (MT) and intermittent pneumatic compression (IPC) are recovery methods used by endurance athletes with little evidence supporting effectiveness. This randomized controlled trial evaluated effectiveness of four daily post-race treatments of a specific MT protocol and IPC compared with supine rest on recovery following an ultramarathon among 56 ultramarathoners. Groups were comparable across all characteristics examined, including post-race plasma creatine kinase concentration. Subject completed timed 400 m runs before the race and on days three, five, seven and 14 post- race, and also provided muscle pain and soreness ratings and fatigue scores immediately before and after treatments, and during the 14 days post- race. Daily subjective measures and 400 m run times were not improved by either treatment, but both treatments reduced (p < .05) muscular fatigue scores acutely after treatment following the race and on post-race day 1, and MT improved (p < .05) muscle pain and soreness acutely following the race.     

The biomechanical functional demand placed on knee and hip muscles of older adults during stair ascent and descent

Age-related decline in physical capabilities may lead to older adults experiencing difficulty in performing everyday activities due to high demands placed on the muscles of their lower extremity. This study aimed to determine the biomechanical functional demand in terms of joint moments and maximal muscle capabilities at the knee and hip joints while older adults performed stair ascent (SA) and stair descent (SD). Eighty-four healthy older adults aged 60-88 years were tested. A torque dynamometer attached to a purpose-built plinth was utilized to measure muscle moments at the knee and hip joints. Participants also underwent full body 3-D biomechanical assessment of stair ascent and descent using an 8-camera VICON system (120 Hz) with 3 Kistler force plates. Stair negotiation required knee extensor moments in excess of the maximum isometric muscle strength available (SA 103%, SD 120%). For the hip, the levels of demand were high, but were slightly lower than those of the knee joint. Stair negotiation placed a high level of demand on the knee extensors with demand in SA reaching maximal isometric capacity and demand in SD exceeding maximal isometric capacity. The levels of demand leave little reserve capacity for the older adult to draw on in unexpected situations or circumstances.     

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Purpose

L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer.

Methods

LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-[¹⁸F]FACBC) PET was assessed for its diagnostic biomarker potential.

Results

Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[¹⁸F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model.

Conclusions

The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[¹⁸F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.     

Complementary information from magnetic resonance imaging and (18)F-fluoromisonidazole positron emission tomography in the assessment of the response to an antiangiogenic treatment in a rat brain tumor model

Introduction

No direct proof has been brought to light in a link between hypoxic changes in glioma models and the effects of antiangiogenic treatments. Here, we assessed the sensitivity of the detection of hypoxia through the use of ¹⁸F-fluoromisonidazole positron emission tomography ([¹⁸F]-FMISO PET) in response to the evolution of the tumor and its vasculature.

Methods

Orthotopic glioma tumors were induced in rats after implantation of C6 or 9L cells. Sunitinib was administered from day (D) 17 to D24. At D17 and D24, multiparametric magnetic resonance imaging was performed to characterize tumor growth and vasculature. Hypoxia was assessed by [¹⁸F]-FMISO PET.

Results

We showed that brain hypoxic volumes are related to glioma volume and its vasculature and that an antiangiogenic treatment, leading to an increase in cerebral blood volume and a decrease in vessel permeability, is accompanied by a decrease in the degree of hypoxia.

Conclusions

We propose that [¹⁸F]-FMISO PET and multiparametric magnetic resonance imaging are pertinent complementary tools in the evaluation of the effects of an antiangiogenic treatment in glioma.     

Comparison of PET-CT and magnetic resonance diffusion weighted imaging with body suppression (DWIBS) for initial staging of malignant lymphomas

Objective

To evaluate the clinical impact of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in staging of malignant lymphoma.

Methods

Twenty-three patients with proven malignant lymphomas were prospectively enrolled. DWIBS (b = 0, 1000 s/mm²) examinations and PET-CT were performed respectively on an Intera 1.5 T unit and a Gyroscan PET-CT scan (Philips Medical system, Best, the Netherland). The criteria for positive node involvement were a size over 10 mm or an apparent diffusion coefficient (ADC) value under 0.75 10⁻³ mm²/s for nodes under 10 mm. For extranodal analysis, a high or heterogeneous signal on DWIBS was considered as positive. In cases of discordance, the reference standard for each region or organ was established at 6 months after the diagnosis according to all available clinical, biological information, as well as histological evidence or follow-up to prove or disprove the presence of disease.

Results

DWIBS and PET-CT results were congruent in 333 node regions on the 345 areas analyzed, with excellent agreement (κ = 0.97, P < 0.0001). From 433 organs analyzed (one patient had splenectomy) extranodal disease was detected in 22 organs on DWIBS. The two imaging techniques agreed on 430 organs (κ = 0.99, P < 0.0001). Finally, Ann Arbor stages based on DWIBS and those of PET/CT were in agreement for 23 patients.

Conclusions

For malignant lymphoma in a pre-therapeutic context, agreement between diffusion-weighted whole-body imaging and PET/CT is high for Ann Arbor staging.