The rise of theranostics: Half 4 — Girls’s theranostics on the horizon

Theranostics is more and more getting used to picture and deal with prostate most cancers and neuroendocrine tumors. Girls’s theranostics seems to already be on the horizon.

A number of presenters on the Society for Nuclear Drugs and Molecular Imaging’s (SNMMI) 2024 assembly in Toronto shared new findings in girls’s research.

CAM-HER2 remedy

Belgium-based Precirix, for instance, highlighted CAM-H2 remedy, a human epidermal development issue receptor 2-directed ligand (HER2) camelid single-domain antibody (sdAb) labeled with radioisotope iodine 131 (I-131).

Referred to as CAM-H2, the focused radioligand remedy is meant for HER2-positive lesions within the therapy of metastatic HER2-positive most cancers indications. Precirix just lately accomplished a examine of CAM-H2 in breast most cancers, gastric most cancers, and gastroesophageal junction most cancers. 

Preliminary knowledge confirmed that CAM-H2 demonstrated excessive affinity for the HER2 goal and fast tissue penetration, defined Josie Gayton, PhD, throughout her presentation at SNMMI. Gayton oversees medical operations at Precirix and serves as the corporate’s chief improvement officer. 

“HER2 remains to be a really main well being burden regardless of the benefits in therapy choices over the previous few years,” Gayton stated throughout her discuss. “With CAM-H2, we engineered the protein to bind to a unique epitope on HER2 to different accepted therapies, so the choice of mixing CAM-H2 with different therapies is certainly a chance.”

The CAM-H2 dose escalation, security, and dosimetry examine in 13 sufferers, largely girls ages 50 to 63, occurred at 4 websites in Canada and the U.S. and included restricted single and cumulative radiation doses. Sufferers included have been HER2-positive (based mostly on earlier historical past) and had been closely pretreated with systemic remedy and exterior beam radiotherapy. 9 had breast most cancers, 4 of whom had mind metastases. Two had gastric most cancers and two had gastroesophageal junction most cancers.

Precirix’s examine examined CAM-H2-1-131 administration at three dose ranges. Sufferers obtained as much as 4 doses of CAM-H2 at 1.85 GBq (50 mCi), 3.7 GBq (100 mCi), and 5.55 GBq (150 mCi) dose ranges given each 4 weeks. 

“If we take into consideration the dose ranges we checked out, the first two cohorts have been very low, subtherapeutic,” Gayton stated. SPECT/CT scans over time confirmed excessive specificity of CAM-H2 in reaching HER2+ lesions and fast uptake of 5 hours with “good retention over time,” particularly in a case of HER2-positive mind metastases nonetheless lighting up at 168 hours (about seven days), Gayton stated. 

Researchers discovered the general security profile acceptable on the administered doses, in keeping with Gayton. As well as, the imply tissue dose didn’t attain the utmost tolerated dose for kidney, bone marrow, or liver. Three grade 3 CAM-H2 therapy emergent hostile occasions (TEAE) have been reported in three sufferers who had a earlier historical past of thrombocytopenia, lung illness, or liver illness, with no grade 4 or 5 hostile occasions reported.

CAM-H2-I-131 is particular, reaches HER2 optimistic lesions, and is retained in lesions for at the very least seven days, in keeping with analysis introduced by Precirix throughout SNMMI 2024.Josie Gayton, PhD, Precirix

Gayton famous, nonetheless, that the examine supplied restricted proof of efficacy; one of the best consequence noticed in three sufferers was confirmed steady illness. 

CAM-H2 methods will likely be evaluated subsequent for section II trials. “The outcomes of this examine assist a proof of mechanism for the single-domain antibody-radioligand platform and will likely be instrumental within the planning of a section II examine of CAM-H2 for therapy of HER2-positive mind metastases,” Gayton stated.

NeoB PET imaging in breast most cancers

Persevering with alongside the HER2 line in girls’s theranostics, sufferers with estrogen receptive optimistic (ER+) and HER2-negative (HER2-) breast most cancers confirmed the highest fee of NeoB-positive illness (90% optimistic in any lesion) within the first outcomes of a potential observational trial of 29 breast most cancers sufferers, in keeping with Dr. David Kersting of the Universitatsmedizin Essen in Germany. 

NeoB can be utilized to determine candidates with ample tumor uptake for Lu-177-NeoB radionuclide remedy. Kersting’s SNMMI 2024 presentation centered on PET imaging utilizing gallium 68 (Ga-68)-NeoB, a novel DOTA-coupled gastrin releasing peptide receptor (GRPR)-targeting antagonist (beforehand referred to as Ga-68-NeoBOMB1), in breast most cancers sufferers.

GRPR is very expressed in breast most cancers as was noticed in 75.8% of 1,432 tissue samples, and in lymph node metastases (94.6%) the place the first tumor was GRPR-positive, in keeping with Kersting.

The examine examined tumor uptake of Ga-68-NeoB on 26 scans in 29 sufferers: 10 from sufferers with newly identified breast most cancers, 16 from sufferers with persistent or recurrent illness, and three from sufferers with out medical verification of an lively tumor. 

Twenty of the 26 scans from sufferers with lively tumors have been NeoB-positive, six NeoB-negative. A region-based evaluation — i.e., breast, lymph node, liver, bone, and different distant metastases — discovered quite a lot of tumor uptake values, Kersting stated. Lymph node and distant metastases confirmed a bent towards greater uptake than breast lesions. Eighteen of the 20 have been ER+/HER2-.

Thus, ER+/HER2- breast most cancers confirmed greater charges of uptake (90% in patient-based evaluation) than sufferers with different hormone receptor standing, Kersting famous. International uptake was bigger than liver uptake (outlined as imply peak tumor-to-liver ratio from all NeoB-positive areas per affected person being bigger than 1) in about two-thirds of ER+/HER2- sufferers.

These findings have been in step with pathology knowledge beforehand printed by different teams, Kersting famous, including that NeoB is a “extremely attention-grabbing goal” in mixture with Lu-177 (Lu-177-NeoB) as a theranostic choice.

Individually, Novartis has a first-in-human examine of Lu-177-NeoB underway to characterize security, tolerability, pharmacokinetics, distribution, radiation dosimetry, and antitumor exercise in sufferers with superior stable tumors identified to overexpress GRPR and with Ga-68-NeoB lesion uptake.

FES PET/CT for preliminary staging of breast most cancers

“There are a number of HER2-targeted PET radiotracers at the moment in medical trials for the detection of HER2-positive malignancy, dedication of illness extent, and collection of sufferers for HER2-targeted remedy,” wrote Gary Ulaner, MD, PhD, director of molecular imaging and remedy at Hoag Household Most cancers Institute, for a assessment and commentary printed June 18 in Radiology.

Ulaner is a professor of radiology and translational genomics. He additionally serves as principal investigator of grants from the Nationwide Institutes of Well being R01, U.S. Division of Protection, and foundations for HER2-, ER-, PSMA-, and CD38-targeted PET radiotracers, in addition to consulting and advising on a number of industrial scientific advisory boards. 

Breast most cancers metastases are sometimes suboptimally detected by present customary of care imaging, which limits optimum therapy choice, Ulaner stated at SNMMI. 

Whereas the fluoroestradiol F-18 radiotracer is accepted by the U.S. Meals and Drug Administration (FDA), it has applicable use standards outlined for it that are extra for serving to to consider sufferers that will likely be hormone-responsive relatively than for staging and for analysis of illness recurrence, Ulaner defined.

“So the worth of FES-PET in preliminary staging of sufferers with domestically superior breast most cancers and within the detection of native recurrence is at the moment unknown,” he stated.

Thus, a section II medical trial was designed for 124 sufferers with ER+ breast most cancers; 62 have been domestically superior newly identified instances, whereas the opposite 62 have been suspected of recurrence based mostly on indicators signs or a laboratory worth. Each teams would bear customary of care imaging, or CT and bone scan, or FDG PET/CT, or FES PET/CT. 

“Wanting on the statistics in each arms of the examine, the FES PET scan was statistically equal to the usual of care arm,” Ulaner defined throughout his SNMMI discuss. Within the newly identified cohort 1, customary of care imaging detected 12/14; FES detected 11/14 (P > 0.99). Within the suspected recurrence cohort 2, customary of care imaging detected 16/23; FES detected 18/23 (P = 0.77).

“This helps the use of FES-PET for sufferers with estrogen receptor-positive breast most cancers at each preliminary staging of domestically superior illness and in sufferers with suspected recurrence, as FES-PET carried out equal to our present requirements of care.” Furthermore, within the sufferers with lobular breast most cancers, FES detected almost twice as many websites of distant metastases or recurrences, Ulaner added. 

Ulaner referred to as the development encouraging. “That is thrilling and represents two novel affected person populations which will profit from FES-PET/CT, which isn’t thought of in these affected person populations,” he stated. “Perhaps extra importantly, there was a development for superiority amongst sufferers with lobular breast malignancies.” 

“This could elevate curiosity in the usage of FES PET/CT for each of those medical indications,” Ulaner informed AuntMinnie.com by way of e mail. Search for full particulars on Ulaner’s examine of ER-targeted PET for preliminary staging and suspected recurrence in ER-positive breast most cancers at JAMA Open on or round July 26. 

Cervical cancer-directed PET

Switching to cervical most cancers, analysis in SNMMI’s highlighted nation South Africa is investigating chemokine receptor CXCR4-directed PET imaging for earlier cervical most cancers detection and deciding on probably simpler remedies.

Cervical most cancers is the main reason behind loss of life for ladies and women from ages 15 to 44 in low and middle-income international locations reminiscent of South Africa, in keeping with SNMMI presenter Bawinile Hadebe, MD, whose staff from the College of KwaZulu-Natal sought to determine the worth of CXCR4-directed PET imaging in sufferers with cervical carcinoma utilizing the radiotracer Ga-68 PentixaFor, in comparison with F-18 FDG.

The small examine concerned 15 girls round 46 years outdated with squamous cell carcinoma and reasonable tumor involvement. Preliminary outcomes confirmed decrease uptake with Ga-68 PentixaFor (detecting 37 lesions) in comparison with F-18 FDG (detecting 68 lesions), in accordance to Hadebe.

“We have to discover options for cervical most cancers in our atmosphere, particularly since our sufferers current late and once they current they typically have already got superior illness and metastatic illness which is difficult to deal with,” Hadebe stated.

In one other examine out of South Africa, College of Pretoria researchers in contrast the Ga-68 fibroblast activation protein inhibitor (FAPI) PET/CT with F-18 FDG PET/CT in imaging most cancers of the cervix. The examine concerned 19 sufferers and located Ga-68 FAPI PET detected extra visceral and skeletal metastases (9 vs 4) and (10 vs 5) in comparison with F-18 FDG PET/CT. Researchers additionally decided Ga-68 FAPI PET has potential for pairing with Lu-177 FAPI in theranostics, in keeping with Kgomotso Mokoala, MD, who introduced on behalf of the work.