Cardiac sympathetic innervation in Parkinson’s disease versus multiple system atrophy

Purpose

The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson’s disease and multiple system atrophy.

Methods

A prospective study including 19 Parkinson’s disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests.

Results

Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson’s disease (p?=?0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson’s disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson’s disease patients (p?<?0.001).

Conclusions

The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson’s disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson’s disease patients.

     

The <Superscript>68</Superscript>Ga/<Superscript>177</Superscript>Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV<Subscript>max</Subscript> values and absorbed dose estimates

Introduction

A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods

Ten consecutive mCRPC patients were selected for ¹⁷⁷Lu-PSMA617 therapy on the basis of PSMA-targeted ⁶⁸Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (⁶⁸Ga-PSMA-HBED-CC and ¹⁸F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1?±?0.3 GBq, range 5.4–6.5 GBq) given intravenously over 30 minutes, 9?±?1 weeks apart. PET/CT scans were compared to ¹⁷⁷Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed.

Results

¹⁷⁷Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4?±?1.9 Gy/GBq; range 1.1–7.2 Gy/GBq), lymph node (2.6?±?0.4 Gy/GBq; range 2.3–2.9 Gy/GBq) as well as liver (2.4?±?0.8 Gy/GBq; range 1.7–3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18?±?0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased ¹⁷⁷Lu-PSMA617 and ⁶⁸Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p?<?0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions.

Conclusion

Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following ¹⁷⁷Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

     

Current status of theranostics in prostate cancer

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of ⁶⁸Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on ⁶⁸Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for ⁶⁸Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, ⁶⁸Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. ⁶⁸Ga-PSMA PET/CT is superior to ¹⁸F / ¹¹Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of ¹⁷⁷Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5–10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that ⁶⁸Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as ²²³Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.     

Current knowledge on the sensitivity of the <Superscript>68</Superscript>Ga-somatostatin receptor positron emission tomography and the SUV<Subscript>max</Subscript> reference range for management of pancreatic neuroendocrine tumours

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three ⁶⁸Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these ⁶⁸Ga-sstr-binding peptides in the imaging setting. On ⁶⁸Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUV_max) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUV_max-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUV_max-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with ⁶⁸Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.     

68Ga-PSMA-11 PET/CT: the rising star of nuclear medicine in prostate cancer imaging?

Wiener Medizinische Wochenschrift - Ever since the introduction of 68Ga-prostate-specific membrane antigen&nbsp;11 positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT)...