18 F-FDG PET/CT allows the direct measurement of metabolic tumor burden in a variety of different malignancies. The aim of this study was to assess whether metabolic tumor volume (MTV) determined by 18 F-FDG PET/CT could be used in the prediction of progression-free and overall survival in multiple myeloma patients. Methods: Forty-seven patients (18 women, 29 men; mean age 6 SD, 63 6 11 y) with stage IIIA disease who had undergone whole-body 18 F-FDG PET/CT were retrospectively evaluated. Images underwent a 3-dimensional region-of-interest analysis including all focal lesions with a maximum standardized uptake value . 2.5. The MTV of each lesion was calculated using an automated contouring program based on the standardized uptake value and developed with a threshold of 40% of the maximum standardized uptake value. The total MTV of each patient was defined as the sum of metabolic volume of all focal lesions. Patients were treated and then subjected to a mean follow-up period of 24 mo. Results: In the 47 patients studied, MTV range was 1.3-316.3 mL, with a median of 23.7 mL. A direct, significant correlation was found between MTV and the percentage of diffuse infiltration of bone marrow by plasma cells (r 5 0.46, P 5 0.006), whereas hemoglobin levels were inversely correlated with MTV (r 5 20.56, P 5 0.0001). At follow-up, patients who developed progressive disease (n 5 18) showed a significantly higher MTV (74.7 6 19.3 vs. 29.8 6 5.1 mL, P 5 0.009) than patients without progressive disease (n 5 29). Furthermore, patients who died of myeloma (n 5 9) had a significantly higher MTV (123.2 6 30.6 vs. 28.9 6 4.2 mL, P 5 0.0001) than survivors (n 5 38). No differences in age, plasma cell infiltration, M protein, albumin, b2-microglobulin, performance status, International Staging System score, and presence or absence of a bone marrow transplant were found between groups. The MTV cutoff level was determined by receiver-operating-characteristic curve analysis, and the best discriminative value found for predicting progression-free and overall survival was 42.2 and 77.6 mL, respectively. By Kaplan-Meier analysis and log-rank testing, progression-free and overall survival at follow-up were significantly better in patients showing an MTV lower than the cutoff than in those having an MTV higher than the cutoff (x 2 5 3.9, P 5 0.04, and x 2 5 56.3, P , 0.0001, respectively). Conclusion: The direct measurement of tumor burden obtained by calculating MTV on 18 F-FDG PET/CT images may be used in the prediction of progression-free and overall survival in myeloma patients.

The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

Purpose: To test whether a novel bifunctional chimeric peptide comprising a cyclic ArgGly-Asp pentapeptide covalently bound to an echistatin domain can discriminate α v β 3 from α v β 5 integrin, thus allowing the in vivo selective visualization of α v β 3 expression by single-photon and positron emission tomography (PET) imaging. Experimental Design: The chimeric peptide was preliminarily tested for inhibition of α v β 3 -dependent cell adhesion and competition of 125