AlphaBet: Combination of Radium-223 and [17 7Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol).

Background: [177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 µm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses. Methods: This is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&T, concurrently with 223Ra in escalating doses (28 kBq/kg - 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&T and the 50% PSA response rate. Conclusion: The AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months. Study registration: NCT05383079.

Do antispasmodics or rectal enemas improve image quality on multiparametric prostate MRI? An 'Evidence-Based Practice' review of the literature.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is increasingly used for the preoperative detection and staging of prostate cancer. Image quality of prostate mpMRI can be significantly degraded by motion related artefact due to bowel peristalsis and susceptibility related artefact, which reduces cancer detection sensitivity. The use of several different methods including anstispasmodic medications and rectal enemas were proposed as potential methods to reduce mpMRI artefacts, but current recommendations in the scientific literature are conflicting and inconsistent. This article seeks to identify the best available evidence to determine which patient preparation method is most effective in improving prostate mpMRI, and provides recommendations for further areas of research. We used the five-step 'Evidence-Based Practice' systematic approach of 'Ask, Search, Appraise, Apply and Evaluate' described by the McMaster University and National Health Service for critical appraisal of topics. We developed a focused clinical question using a PICO format, and performed a primary and secondary literature search through Ovid Medline, Ovid Embase and Cochrane CENTRAL (Wiley). All identified articles were appraised for strength and validity. Seven articles were retrieved which demonstrated conflicting sensitivities and specificities for intravenous hyoscine butylbromide and rectal enema in improving image susceptibility artefact, motion artefact, and anatomic distortion on the T2 or diffusion weighted imaging sequences. Intravenous hysoscine butylbromide is the optimum patient preparation method for improving T2W and DWI image quality in prostate mpMRI. The use of a preparatory rectal enema is not currently recommended, but better quality studies are required.

Coronary artery bypass graft imaging with 64-slice multislice computed tomography: literature review.

Recurrent cardiac ischemia after coronary artery bypass graft surgery occurs in a significant proportion of patients, prompting repeat investigations and incurring significant clinical and financial costs. Noninvasive investigations to identify graft occlusion and quantify graft stenosis are desirable due to the complications, cost, and patient inconvenience of invasive coronary angiography. The increasing use of 64-slice multislice computed tomography has led to multiple reports on its accuracy in graft stenosis and occlusion. This review focuses on image acquisition and manipulation techniques, interpretative pitfalls, and the diagnostic performance of 64-slice multislice computed tomography in coronary artery bypass graft imaging across the medical literature.

Coronary stent assessment with 64-slice multislice computed tomography: a literature review.

Coronary in-stent restenosis (ISR) and thrombosis cause recurrent cardiac ischemia, require repeat investigations, and have significant clinical and financial implications. As coronary stenting becomes widespread, the number of patients with recurrent ischemia is increasing. ISR and thrombosis occur in up to 10 and 0.8%, respectively, of patients with drug-eluting stents. A noninvasive investigation for symptomatic stented patients is required to identify stent thrombosis, ISR, and de novo lesions in native coronary arteries. The difficulties in using computed tomography to image high-density materials adjacent to moving calcified vessels have been reduced with advances in spatial and temporal resolution and reconstruction software. This review examines the advantages and disadvantages of 64-slice multislice computed tomography for coronary stent evaluation, explaining the diagnostic difficulties and outlining techniques to optimize diagnostic accuracy.