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Objective A test-retest cohort study was conducted to assess the use of a novel computer-aided, combined movement examination (CME) to measure change in low back movement after pain management intervention in 17 cases of lumbar spondylosis. Additionally we desired to use a CME normal reference range (NRR) to compare and contrast movement patterns identified from 3 specific structural pathologic conditions: intervertebral disc, facet joint, and nerve root compression. Methods Computer-aided CME was used before and after intervention, in a cohort study design, to record lumbar range of movement along with pain, disability, and health self-report questionnaires in 17 participants who received image-guided facet, epidural, and/or rhizotomy intervention. In the majority of cases, CME was reassessed after injection together with 2 serial self-reports after an average of 2 and 14 weeks. A minimal clinically important difference of 30% was used to interpret meaningful change in self-reports. A CME NRR (n = 159) was used for comparison with the 17 cases. Post hoc observation included subgrouping cases into 3 discrete pathologic conditions, intervertebral disc, facet dysfunction, and nerve root compression, in order to report intergroup differences in CME movement. Results Seven of the 17 participants stated that a “combined” movement was their most painful CME direction. Self-report outcome data indicated that 4 participants experienced significant improvement in health survey, 5 improved by ≥30% on low back function, and 8 reported that low back pain was more bothersome than stiffness, 6 of whom achieved the minimal clinically important difference for self-reported pain. Subgrouping of cases into structure-specific groups provided insight to different CME movement patterns. Conclusion The use of CME assists in identifying atypical lumbar movement relative to an age and sex NRR. Data from this study, exemplified by representative case studies, provide preliminary evidence for distinct intervertebral disc, facet joint, and nerve root compression CME movement patterns in cases of chronic lumbar spondylosis. [ABSTRACT FROM AUTHOR]

Background: Interspinous spacer/implants like the Device for Intervertebral Assisted Motion (DIAM™) are controversially yet commonly used in the surgical treatment of lumbar degenerative pathologies. Criticism is based on ill-defined indications, lack of superiority over decompression, and a poorly understood mechanical effect. Yet, continued use by surgeons implies their perceived clinical merit. We examined radiographic spinal alignment for 12 months, and pain and function for 24 months, after DIAM-augmented surgery to improve the understanding of the mechanical effect relating to clinical outcomes in patients. Methods: We undertook a single-surgeon prospective, longitudinal study of 40 patients (20 F, 20 M) who received DIAM-augmented surgery in treatment of their symptomatic lumbar degenerative condition. Outcomes measured included sagittal spinal alignment (lumbar lordosis, sacral inclination, primary (PDA), supradjacent (SDA) disc angles, and regional sagittal balance (RSB; standing lateral radiographs), and back and leg pain (visual analogue scale; VAS) and function (Oswestry Disability Index; ODI). Responders were identified as those with clinically meaningful improvement to pain (>20%) and function (>15%) at 24 months postoperatively; features of sagittal spinal alignment between responders and non-responders were examined. Results: Sagittal alignment was unchanged at 12 months. At 6 weeks postoperatively, PDA (mean (SD)) reduced by 2. 2° (4.0°; p < 0.01) and more-so in back pain non-responders (3.8° (3.2°)) than responders (0.7° (4.4°); p <0.05).Positive preoperative RSB in responders (26.7Rmm (42.3Rmm); Rmm is a system-relative measure) decreased at 6 weeks (by 3. 1Rmm (9.1Rmm)). Non-responders had a negative RSB preoperatively (-1.0Rmm (32.0Rmm)) and increased at 6 weeks (11.2Rmm (15.5Rmm); p < 0.05). Clinically meaningful improvement for the whole cohort for back pain and function were observed to 24 months (back pain: 25.0% (28.0); function: 15.4% (17.6); both p < 0.0001). Conclusions: Unaltered sagittal alignment at 12 months was not related to symptoms after DIAM-augmented lumbar surgery. Subtle early flattening at the index disc angle was not maintained. Preoperative and early post-operative sagittal alignment may indicate response after DIAM-augmented surgery for mixed lumbar pathologies. Further investigation toward defining indications and patient suitability is warranted. [ABSTRACT FROM AUTHOR]

New macrobicyclic cage amine or “sarcophagine” (sar) bifunctional chelators have been synthesised that form copper complexes of exceptional in vivo stability and incorporate isothiocyanate (-NCS) functional groups for conjugation to an antibody. The chelators were synthesised from the methyl-capped complex [MgII(CH3)(NH2)sar]2+. Coordination of MgII within the cavity of the cage amine ligand protects the secondary amine atoms from reacting with the -NCS functional groups. Two different [MgII(NCS-sar)]2+ derivatives were conjugated to the HER2/neu-targeting antibody trastuzumab and the progress of the reaction monitored by electrospray mass spectrometry. The MgII ion was removed from the immunoconjugates under mild conditions (0.1 M citrate buffer, pH 6). Labelling of the (CH3)(p-NCS-Ph)sar-trastuzumab conjugate with 64CuII, a radioisotope suitable for positron emission tomography (PET), was fast (∼5 min) and easily performed at room temperature with high radiochemical purity (＞95%). Biodistribution and PET imaging studies in vivo showed that 64Cu-labelled (CH3)(p-NCS-Ph)sar-trastuzumab maintained high stability under physiological conditions with high and selective uptake in a HER2-positive cancer cell line. The stability of the copper complex and the 12.7 h half-life of the radioisotope allows clear visualisation of tumours out to 48 h. [ABSTRACT FROM AUTHOR]

The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFvanti-LIBS targets ligand-induced binding sites (LIBS) on the glycoprotein receptor GPIIb/IIIa, which is present on activated platelets. The immunoconjugates were radiolabeled with the positron-emitting isotope 64Cu. The new radiolabeled conjugates were shown to bind selectively to activated platelets. The diagnostic potential of the most promising conjugate was demonstrated in an in vivo model of carotid artery thrombosis using positron emission tomography. This approach gives homogeneous products through site-specific enzyme-mediated conjugation and should be broadly applicable to other metal complexes and proteins. [ABSTRACT FROM AUTHOR]

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding CuII with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl- 3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr3-octreotate. Radiolabeling of SarTATE with 6CuII, a radioisotope suitable for positron emission tomography (PET), was fast (∼20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of 64CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between 64CuSarTATE and 64Cu-labeled DOTA-Tyr3-octreotate (64CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of 64CuDOTATATE decreased significantly at 24 h, 64CuSarTATE activity was retained, improving contrast at later time points. 64CuSarTATE accumulated less than 64CuDOTATATE in the nontarget organs, liver and lungs. The uptake of 64CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr3-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of 64Cu- and 67CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to 64CuDOTATATE at longer time points. [ABSTRACT FROM AUTHOR]

Purpose: The device for intervertebral assisted motion (DIAM™) is an interspinous (ISP) implant used to augment surgical decompression of lumbar degenerative conditions: Lumbar spinal stenosis [LSS; foraminal (FS) or central canal (CS)], herniated and degenerated disc disease, facet joint pain syndrome (FJPS) and minor degenerative spondylolisthesis (DS). Limited evidence guides its use in defined clinical indications, while few studies demonstrate effect according to clinically meaningful change (MCID). This prospective longitudinal study examined the efficacy of DIAM-augmented decompression surgery in the broad application of a single-center clinical reality. Methods: Eighty-one consecutive cases [37F, 44M; 52 years (SD 13)] were examined for two years after DIAM-augmented decompression surgery. Patient-reported pain [back and leg; visual analogue scale (VAS)], function [Oswestry disability index (ODI)], and satisfaction (Likert scale) were serially examined and referenced to contemporary MCID thresholds. Subjects were classified into anatomical and diagnostic categories and analyzed according to subgroups to better inform clinical pathways. Serial change was assessed with Scheffe post-hoc test; change scores with unpaired t-tests and descriptive statistics (p < 0.05). Results: Subjects reported 20.4% (SD 29.5; p < 0.0001) mean improvement in back pain, 20.3% (SD 30.6; p < 0.0001) in leg pain, and 15.1% (SD 20.8; p < 0.0001) in function at two years postoperatively. Greatest improvement was seen at six weeks for back pain (by 30.5%; p < 0.0001) and leg pain (by 29.4%; p < 0.0001) and three months for function (by 18.7%; p < 0.0001). Leg pain deteriorated between six weeks and 18 months (p < 0.05). There were more responders at one compared to two years after surgery. FS cases showed superior improvement compared to DS subjects (p < 0.05). Cases receiving multiple adjunctive surgical decompressions in addition to their DIAM had superior improvement than those receiving a single procedure (p < 0.05). Conclusions: Clinical improvement in back pain, leg pain and function were achieved to two years in a single-center cohort of 81 cases with lumbar degenerative disease who received DIAM-augmented decompression surgery. Subsets of the sample had a superior sustained response including foraminal/lateral recess stenosis patients and cases treated with > 1 adjunctive decompression techniques. The need for assessing homogeneous cohorts in future studies is emphasized. [ABSTRACT FROM AUTHOR]

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6610-8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6610-13; SOX6, p = 6.4610-10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation. [ABSTRACT FROM AUTHOR]

Interspinous implants (ISP) represent a contemporary non-fusion surgical option in the treatment of lumbar segment disease. Several devices have been developed within the last two decades and have been variously supported by investigations into their clinical and biomechanical efficacy. Spinal stenosis and facet arthropathy are reported as the primary clinical indications for their use, with degenerative disc disease and segmental instability recently extending their application. The principle common to all interspinous systems is an induced distraction of the interspinous space, resulting in reduced approximation of pain-sensitive and space-occupying tissue. Collectively, these devices are considered to prevent adjacent segment overload by restoring physiologic load transmission. This review article summarizes existing published literature, describes four different interspinous implants — the DIAM, Wallis, X-Stop and Coflex systems, and outlines clinical trials in progress. The design and surgical technique characteristics, mechanism of action, and clinical indications for interspinous implants are reviewed. Recommendations for future research of interspinous implants in the treatment of lumbar segment disease are made. [ABSTRACT FROM AUTHOR]

Posterior interspinous dynamic stabilization is used increasingly in the treatment of lumbar degenerative spinal conditions, with preliminary evidence for its clinical and biomechanical efficacy emerging. The need remains to define patients who respond best to this form of surgery. This study examined clinical outcomes in 39 patients (21 females) with defined lumbar spinal pathologies, for two years after lumbar surgery augmented with the Device for Intervertebral Assisted Motion (DIAM). Anatomical patient categorization revealed involvement of disc (n=25/39) and facet (n=14/39) lumbar pathology, with clinical indications for surgery being: segmental instability (n=21/39); nerve root compression (n=11/39); and facet joint pain syndrome (n=7/39). Pain, function and satisfaction data were derived from MODEMS self-report questionnaires, which were collected prospectively over a two-year post-operative period. Results showed that L4-5 and L5-S1 were the most common DIAM-implanted spinal levels. Clinically significant post-operative improvement in pain (23.4%) and function (13.5%) occurred between three and twenty-four months. Eleven (of 39) required further lumbar surgery. Nineteen (of 28) were more satisfied at 24 months post-operatively compared to baseline. Disc involvement and segmental instability were the most common presenting lumbar segmental pathologies, yet the least successful in response to surgery augmented with DIAM. Patients with facet involvement reported superior improvement post-operatively compared with those with disc involvement. Patients with facet joint disease demonstrate better outcomes at 24 months following lumbar surgery augmented with DIAM posterior interspinous dynamic stabilization, compared with those presenting with disc pathology. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates how femoral geometry in older women is affected by modifiable lifestyle variables, physical activity (PA), and calcium intake (CI). The study measured femoral geometry, PA, and CI were measured through a sample of 1008 women who participated in a randomized controlled trial of calcium supplementation. According to the results, both CI and PA have favorable association with bone structural geometry.

SUMMARY Segmental variations in vertebral body cancellous bone architecture throughout the thoracolumbar spine were examined using histomorphometry and microradiography, and compared to bone mass measured using dual energy X-ray absorptiometry. In six human vertebral columns (T1 to L5) bone mineral content (BMC) and bone mineral density (BMD) of each vertebral body was determined in the lateral projection. Sagittal plane cancellous bone architecture was assessed from two-dimensional surface stained images and microradiographs of two 1 mm thick sections at each vertebral level. Computer-assisted image analysis was used to measure the total bone area (TBA), mean trabecular width (MTW) and trabecular number (TbN) from the stained images, and the skeletonized network length (SNL) from the radiographic images. Consistent segmental trends were observed for all structural parameters across the six columns examined. Higher TBA and TbN values were observed in the upper thoracic segments and decreased caudally. The MTW was relatively constant in the thoracic vertebrae before increasing in the lumbar spine. Pooled correlations between TBA and the bone density measurements were poor (BMC: r=0.17, BMD: r= 0.25), while the TBA and SNL were only moderately correlated ( r= 0.42). In conclusion, histomorphometric and radiological measurements appear to provide different information about cancellous bone structure. Bone structure is poorly correlated to integral measurements of bone mass. The consistent segmental variations in bone architecture appear to reflect a skeletal response to the relative extent of habitually applied loads in different regions of the spine. [ABSTRACT FROM AUTHOR]

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.661028), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6610213; SOX6, p = 6.4610210) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation.

Abstract: Hip structural analysis (HSA) is a technique for extracting strength-related structural dimensions of bone cross-sections from two-dimensional hip scan images acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the precision of the method has not been thoroughly tested in the clinical setting. Using paired scans from two large clinical trials involving a range of different DXA machines, this study reports the first precision analysis of HSA variables, in comparison with that of conventional bone mineral density (BMD) on the same scans. A key HSA variable, section modulus (Z), biomechanically indicative of bone strength during bending, had a short-term precision percentage coefficient of variation (CV%) in the femoral neck of 3.4–10.1%, depending on the manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a determinant of bone strength during axial loading and closely aligned with conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%. Poorer precision was associated with inadequate inclusion of the femoral shaft or femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between 1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The precision of HSA variables was not generally dependent on magnitude, subject height, weight, or conventional femoral neck densitometric variables. The generally poorer precision of key HSA variables in comparison with conventional DXA-derived BMD highlights the critical roles played by correct limb repositioning and choice of an adequate and appropriately positioned ROI. [Copyright &y& Elsevier]

The aim of this preclinical study was to directly compare 18F]PSMA-1007 with both 68Ga]Ga-PSMA-11 and 18F]AlF-PSMA-11 in mice bearing PSMA-positive tumor xenografts. Uptake was assessed by PET/CT at 1, 2 and 4 h post-injection, and by ex vivo measurement after 4 h. 18F]PSMA-1007 demonstrated the highest tumor uptake of the three tracers. The high uptake in bone for mice injected with 18F]AlF-PSMA-11 suggested rapid in vivo decomposition. This was confirmed by an in vitro plasma stability study. • The uptake of 18F]PSMA-1007, 68Ga]Ga-PSMA-11 and 18F]AlF-PSMA-11 were compared. • 18F]PSMA-1007 demonstrated the highest tumor uptake of the three tracers. • 18F]AlF-PSMA-11 demonstrated low uptake in tumor and high uptake in bone. • The instability of 18F]AlF-PSMA-11 in plasma confirmed rapid in vivo degradation. [ABSTRACT FROM AUTHOR]

New macrobicyclic cage amine or "sarcophagine" (sar) bifunctional chelators have been synthesised that form copper complexes of exceptional in vivo stability and incorporate isothiocyanate (-NCS) functional groups for conjugation to an antibody. The chelators were synthesised from the methyl-capped complex [Mg(II)(CH3)(NH2)sar](2+). Coordination of Mg(II) within the cavity of the cage amine ligand protects the secondary amine atoms from reacting with the -NCS functional groups. Two different [Mg(II)(NCS-sar)](2+) derivatives were conjugated to the HER2/neu-targeting antibody trastuzumab and the progress of the reaction monitored by electrospray mass spectrometry. The Mg(II) ion was removed from the immunoconjugates under mild conditions (0.1 M citrate buffer, pH 6). Labelling of the (CH3)(p-NCS-Ph)sar-trastuzumab conjugate with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (∼5 min) and easily performed at room temperature with high radiochemical purity (>95%). Biodistribution and PET imaging studies in vivo showed that (64)Cu-labelled (CH3)(p-NCS-Ph)sar-trastuzumab maintained high stability under physiological conditions with high and selective uptake in a HER2-positive cancer cell line. The stability of the copper complex and the 12.7 h half-life of the radioisotope allows clear visualisation of tumours out to 48 h.

We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.

The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFv(anti-LIBS) targets ligand-induced binding sites (LIBS) on the glycoprotein receptor GPIIb/IIIa, which is present on activated platelets. The immunoconjugates were radiolabeled with the positron-emitting isotope (64)Cu. The new radiolabeled conjugates were shown to bind selectively to activated platelets. The diagnostic potential of the most promising conjugate was demonstrated in an in vivo model of carotid artery thrombosis using positron emission tomography. This approach gives homogeneous products through site-specific enzyme-mediated conjugation and should be broadly applicable to other metal complexes and proteins., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.