Abstract:The aim of this study was the evaluation of (68)Ga-DOTA-E-[c(RGDfK)](2) as a novel PET tracer to image αvβ3 and αvβ5 integrins. For this purpose, DOTA-E-[c(RGDfK)](2) was labeled with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator, purified by solid-phase extraction and the radiochemical purity analyzed by radio-RP-HPLC. (68) Ga-DOTA-E-[c(RGDfK)](2) was obtained reproducibly in radiochemical yields of 60 ± 6% and with an excellent radiochemical purity of >99%. In nude rats bearing bone metastases af… Show more
“…In an experimental study [ 68 Ga] DOTA-E-[c(RGDfK)] 2 was shown to be a promising novel PET tracer suitable for the imaging of αvβ3 and αvβ5 integrins which are overexpressed in bone metastases. The tracer featured rapid and specific uptake into these metastases and fast blood clearance, rendering it an interesting target for detection and follow-up of osseous metastases ( Figure 2 ; [38] ). Figure 2 (A) Three-dimensional volumetric computed tomography reconstruction of the pelvis and the hind legs of the same animal (upper reconstruction: anterior-posterior; lower reconstruction: posterior-anterior); (B) coronal μPET image (single frame) of a nude rat bearing a bone metastasis after the injection of [ 68 Ga] DOTA-E-[c(RGDfK)] 2.…”
SummaryMetastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.
“…In an experimental study [ 68 Ga] DOTA-E-[c(RGDfK)] 2 was shown to be a promising novel PET tracer suitable for the imaging of αvβ3 and αvβ5 integrins which are overexpressed in bone metastases. The tracer featured rapid and specific uptake into these metastases and fast blood clearance, rendering it an interesting target for detection and follow-up of osseous metastases ( Figure 2 ; [38] ). Figure 2 (A) Three-dimensional volumetric computed tomography reconstruction of the pelvis and the hind legs of the same animal (upper reconstruction: anterior-posterior; lower reconstruction: posterior-anterior); (B) coronal μPET image (single frame) of a nude rat bearing a bone metastasis after the injection of [ 68 Ga] DOTA-E-[c(RGDfK)] 2.…”
SummaryMetastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.
“…The results showed that all the primary tumor and metastasis were clearly identified although the standard uptake values were heterogeneous, suggesting varying levels of α
v
β
3 overexpression (Figure 4). Mühlhausen et al reported 68 Ga-DOTA-E-[c(RGDfK)] as a PET tracer suitable for monitoring bone metastases in a breast cancer mouse model [76]. …”
Section: Molecular Probes For Imaging Breast Cancer Specific Targetsmentioning
Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.
“…Previous in vitro experiments with an alternative positron emission tomography (PET) α v β 3 integrin targeting tracer, 64 Cu-CB-TE2A-c(RGDyK), have shown specific uptake in osteoclasts and a correlation with osteoclast numbers in a mouse model of parathyroid hormone-induced osteolysis in the calvaria [ 8 ]. Similarly, the same PET tracer has shown specific uptake in a mouse model of osteolytic bone metastases [ 9 ], and a different PET tracer, 68 Ga-DOTA-E-[c(RGDfK)] 2 , has shown specific accumulation in a rat model of breast cancer bone metastasis [ 13 ]. In humans, a different 99m Tc-RGD tracer ( 99m Tc-3PRGD2) has been shown to detect bone metastases from lung cancer with high sensitivity and with better specificity than 99m Tc-methylene diphosphonate scintigraphy [ 14 ].…”
PurposeOsteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of 99mTc-maraciclatide, a radiopharmaceutical targeting αvβ3 integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy.MethodsThe study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with 99mTc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria.ResultsBefore treatment, metastases showed specific 99mTc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389–740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46–381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and −8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (−21.9, and −27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = −0.59, p = 0.006).Conclusions99mTc-maraciclatide accumulates in PCa bone metastases in keeping with increased αvβ3 integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and 99mTc-maraciclatide imaging may be a potential method for assessing early response.
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