AI News, New type of PET imaging identifies primary and metastatic prostate cancer
- On 6. juni 2018
- By Read More
New type of PET imaging identifies primary and metastatic prostate cancer
The new agent is a gallium-68 (Ga-68)-labeled peptide BBN-RGD agent that targets both gastrin-releasing peptide receptor (GRPR) and integrin ?v?3.
Dual-receptor targeting provides advantages over single-receptor targeting by allowing tumor contrast when either or both receptor types are expressed, improving binding affinity and increasing the number of effective receptors.
'An effective and specific imaging method of detecting both primary and metastatic lesions is thus of critical importance to manage patients with prostate cancer.'
'Compounds capable of targeting more than one biomarker have the ability of binding to both early and metastatic stages of prostate cancer, creating the possibility for a more prompt and accurate diagnostic profile for both primary and the metastatic tumors,' explains Chen.
Looking ahead, Chen says, 'Ga-68-BBN-RGD could play an additive role in staging and detecting prostate cancer and provide guidance for internal radiation therapy using the same peptide labeled with therapeutic radionuclides.'
Prostate-specific membrane antigen as a target for cancer imaging and therapy
A recent prospective study in patients awaiting prostatectomy found that this agent was able to identify tumors with a Gleason score of 7 or greater.122 A phase I imaging trial with a 89Zr-labeled, engineered fragment of J591 (89Zr-huJ591) in 10 patients with metastatic prostate cancer demonstrated the ability of this construct to identify metastases, including lesions that were not noted on conventional imaging.123 One of the primary shortcomings of antibody-based imaging is the long time from injection to optimal imaging time, with several days often required.
Among the early small-molecule PSMA ligands tested in human subjects were a pair of 123I-labeled agents, 123I-MIP-1072 and 123I-MIP-1095, which have been found to localize to sites of metastatic prostate cancer in both bone and soft tissue.71 Agents 99mTc-MIP-1404 and 99mTc-MIP-1405 (Table II, Entry 10) were investigated in six healthy men and six men with radiographic evidence of metastatic prostate cancer.124 Compared to standard MDP bone scanning, both agents identified most bone metastatic lesions and rapidly detected soft-tissue lesions including sub-centimeter lymphnodes.
A study of 37 patients with biochemically recurrent prostate cancer demonstrated a higher lesion detection rate with 68Ga-PSMA PET/CT in comparison to 18F-fluoromethylcholine PET/CT.131 A large retrospective analysis of 319 patients with biochemical recurrence found that 68Ga-PSMA was able to detect sites of disease in 82.8%, with reported sensitivity, specificity, negative predictive value, and positive predictive value on a lesion-by-lesion basis of 76.6%, 100%, 91.4%, and 100%, respectively.132 A separate retrospective analysis of 248 patients with biochemical recurrence demonstrated similar findings, with 89.5% of patients being found to have radiotracer-avid sites of disease.133 In addition to those larger studies, case reports have been published demonstrating the ability of 68Ga-PSMA to detect a brain metastasis due to prostate cancer,134 to be used with MR imaging for the detection of primary disease,135, 136 and to evaluate the response of bone metastases to 223Ra therapy.137 Although both 18F- and 68Ga-labeled small-molecule radiotracers for PSMA have demonstrated excellent promise, a recent manuscript by Dietlein et al.
New radiotracer could make diagnosing prostate cancer faster and easier
Researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have developed a new radiotracer to diagnose prostate cancer and conducted a successful Phase I clinical trial.
Like a key fitting into a lock, the carrier molecules bind to certain receptors or biomarkers and the radioactive atoms enable PET or SPECT scanners to image areas where the tracers have collected in large numbers.
“Targeting multiple biomarkers could potentially allow us to identify prostate cancer at its early stages as well as after metastasis in one scan.” Chen believes that dual-receptor targeting tracers could one day be the primary method for diagnosing and monitoring prostate cancer reducing the amount of medical scans a patient would be forced to undergo and streamlining the diagnostic and therapeutic process.
<?xml version="1.0" encoding="UTF-8"?>Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter–Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth
and radioisotope therapy (radium-223) although have shown promising results in delaying skeletal complications and also improving overall survival , the management of patients with metastatic CRPC remains a challenge, with a mean survival time of less than 19 months .
However, recent studies have evidenced the intricate intercellular communication between stromal and cancer epithelial cells leading to permanent genetic and behavioral changes not only in the epithelial cells but also in cancer-associated stromal cells that drives further genetic and gene expression changes in prostate cancer cells [5, 6].
Through a series of complex, intimate bi-directional communications between prostate cancer and the host stroma, cancer cells gain additional growth and survival advantages and ultimately disseminate to distant organs with lethal effect [7–9].
Osteonectin (also known as basement membrane-40 [BM-40] and secreted protein acidic rich in cysteine [SPARC]) is widely distributed in several tissues during development and cellular injury  and plays a major role in regulating cell adhesion, proliferation, migration, and tissue remodeling .
In addition, elevated osteonectin levels in primary prostate cancer was associated with the subsequent development of metastasis , indicating that prostate cancer cell metastasis to the bone is mediated in part by the osteonectin-mediated promotion of cancer cell migration, protease activity, and invasion.
Because osteonectin expression occurs in both tumor epithelial cells and bone cells, the osteonectin promoter could be used to drive a therapeutic gene co-targeting the bone metastatic prostate cancer and its supporting microenvironment, regardless of the basal level of AR and PSA expression.
- On 6. juli 2020
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