Randomized trial to assess change in left ventricle ejection fraction (LVEF) and myocardial perfusion in patients with acute myocardial infarction (AMI) of anterior wall treated with bone marrow stem cells (BMSCs), compared with control group—from baseline in the acute phase up to 12 months of follow-up. Forty-five patients were randomized 2:1 to BMSC group (n= 31) or to control group (n = 14). Bone marrow stem cells were administered into infarct-related artery (IRA) at 4–6 day after primary PCI. Groups were followed up with Tc-99m-MIBI SPECT, radionuclide ventriculography (EF-RNV), echocardiography (ECHO), and spiroergometric stress test. Coronary angiography was repeated after 6 months. EF-RNV did not differ significantly in both groups, but trend towards increase in EF at 6 months and its maintenance after 12 months was noticed in the BMSC group. At rest study, perfusion index (PI) of region supplied with blood by IRA distal to its previous occlusion (PI-IRA) improved significantly in the BMSC group at 6 months: PI-IRA at 4–6 days vs. PI-IRA at 6 months (3.00 ± 0.97 vs. 2.65 ± 0.64; P = 0.017). At 12 months, PI-IRA at rest was 2.66 ± 0.55; P = 0.07. The difference between BMSC and control groups at rest study in PI-IRA was not observed. At dipyridamole study (PI-dip), perfusion in the BMSC group was better compared with controls at 6 months (2.26 ± 0.44 vs. 2.47 ± 0.40; P = 0.033) and at 12 months (2.34 ± 0.55 vs. 2.52 ± 0.42; P = 0.014), also for region supplied with blood by IRA (PI-IRA-dip; at 6 months 2.63 ± 0.77 vs. 3.06 ± 0.46; P = 0.021 and at 12 months 2.71 ± 0.63 vs. 3.15 ± 0.51; P = 0.001). Results of LVEF, LVEDV, LVESV in ECHO and results of spiroergometric stress test did not differ significantly between groups. Major adverse cardiac events occurred more often in the control group (P = 0.027). In our study, BMSC intracoronary transplantation in patients with anterior AMI did not result in increase in EF. Slight improvement of myocardial perfusion was noticed in the BMSC group. This finding may indicate better microcirculation enhanced by BMSCs, but small number of patients allow for hypothesis rather than final statement.
Significant advances have been made in thyroid cancer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines “Diagnostics and Treatment of Thyroid Carcinoma” have been formulated at the “Thyroid Cancer and Other Malignancies of Endocrine Glands” conference held in Wisła in November 2015 [1]. Significant advances have been made in thyroid cancer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines “Diagnostics and Treatment of Thyroid Carcinoma” have been formulated at the “Thyroid Cancer and Other Malignancies of Endocrine Glands” conference held in Wisła in November 2015 [1].
Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DGA-DPhe6,Sar11,LeuNHEt13]BBN(6-13); N4: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC50 = 0.37 ± 0.03 nM) and [99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies.
18 November 2014 in Archivum Immunologiae et Therapiae Experimentalis
In rare cases of differentiated thyroid carcinoma (DTC), radioiodine treatment is no longer effective due to cell dedifferentiation. Targeting somatostatin receptors in DTC cells by radiolabelled somatostatin analogues could provide an alternative therapy option. The aim of this study was to evaluate safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced, non-iodine avid DTC. Eleven patients aged 47–81 years (median: 65 years) with a history of several courses of radioiodine therapy, increasing thyroglobulin (Tg) and negative whole body scan, were qualified to the study. After confirming receptor expression by somatostatin receptor scintigraphy, PRRT with yttrium-90 labelled analogue was initiated. Fractionated treatment protocol was used with four doses of 90Y-DOTA-TOC in 12-week intervals. Activity of each dose was 3.7 GBq (100 mCi). Of 11 patients, 5 died before receiving the fourth course of PRRT. In the remaining six patients, morphological response, evaluated 3 months after the last course using RECIST criteria showed partial remission (PR) in one patient, stable disease (SD) in two patients and progressive disease (PD) in three patients. Biochemical response based on Tg measurements before and after PRRT showed PR in one patient, SD in four patients and PD in one patient. Median survival was 21 months from the first course of PRRT. Only minor and transient hematological toxicity was observed in some patients. We conclude that PRRT is generally well-tolerated and may be a valuable option for some patients with radioiodine-refractory DTC.
Glutamate carboxypeptidase II (GCP), also known as prostate specific membrane antigen (PSMA) has been found to be expressed in glioma vasculature in in-vitro studies. GCP expression can be traced with the use of [68Ga]Ga-PSMA-11 PET/CT used routinely for prostate cancer imaging. The aim of this paper was to analyze GCP expression in the recurrent glial tumors in vivo. 34 patients (pts.) aged 44.5 ± 10.3 years with suspicion of recurrence of histologically confirmed glioma grade III (6 pts.) and grade IV (28 pts.) were included in the study. All patients underwent contrast-enhanced MR and [68Ga]Ga-PSMA-11 PET/CT. No radiopharmaceutical-related adverse events were noted. PET/CT was positive in all the areas suspected for recurrence at MR in all the patients. The recurrence was confirmed by histopathological examinations or follow-up imaging in all cases. The images showed a very low background activity of the normal brain. Median maximal standard uptake value (SUVmax) of the tumors was 6.5 (range 0.9–15.6) and mean standard uptake value (SUVmean) was 3.5 (range 0.9–7.5). Target-to-background (TBR) ratios varied between 15 and 1400 with a median of 152. Target-to-liver background ratios (TLR) ranged from 0.2 to 2.6, the median TLR was 1.3. No significant difference of the measured parameters was found between the subgroups according to the glioma grade. High GCP expression in the recurrent glioma was demonstrated in-vivo with the use of [68Ga]Ga-PSMA-11 PET/CT. As the treatment options in recurrent glioma are limited, this observation may open new therapeutic perspectives with the use of radiolabeled agents targeting the GCP.