Imaging αvβ3 integrin expression in skeletal metastases with 99mTc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment

Abstract

PurposeOsteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of 99mTc-maraciclatide, a radiopharmaceutical targeting αvβ3 integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy.MethodsThe study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with 99mTc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria.ResultsBefore treatment, metastases showed specific 99mTc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389–740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46–381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and −8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (−21.9, and −27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = −0.59, p = 0.006).Conclusions99mTc-maraciclatide accumulates in PCa bone metastases in keeping with increased αvβ3 integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and 99mTc-maraciclatide imaging may be a potential method for assessing early response.

Functional and Hybrid Imaging of Bone Metastases

“…In man, radiolabeled RGD compounds have shown accumulation in bone metastases from lung cancer and also prostate cancer . In the latter report, an inverse correlation was seen between lesion uptake and CT density in keeping with an osteoclastic mechanism of uptake. A reduction in activity was also noted in patients who responded to systemic treatment with abiraterone compared to those who had progressive disease.…”

“…Preclinical experiments in osteolytic metastatic and PTHrP‐induced calvarial models have demonstrated osteoclast‐specific accumulation . In man, radiolabeled RGD compounds have shown accumulation in bone metastases from lung cancer and also prostate cancer . In the latter report, an inverse correlation was seen between lesion uptake and CT density in keeping with an osteoclastic mechanism of uptake.…”

SPECT/CT: Standing on the Shoulders of Giants, It Is Time to Reach for the Sky!

“…Providing a very early readout of treatment effect, it could potentially be used to tailor cancer treatments more quickly, sparing toxicity and cost in nonresponding patients (53). Another interesting target in oncology and cardiovascular medicine is angiogenesis, with 99m Tc-HYNIC-L(arginine-glycine-aspartate) or 99m Tc-maraciclatide integrin a v b 3 imaging demonstrating the ability to visualize tumors and treatment response in cancer models (54). Integrin imaging has also been used to visualize inflamed atherosclerotic plaques, with the potential to noninvasively identify high-risk plaques in patients (55).…”

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

“…112 In addition to galactose-labeled RGD, researchers also use 99 mTc, bombesin, gastrin-releasing peptide receptor and RGD labeled with Afterglow materials to track PCa progression. [113][114][115] According to their results, after chemical-or biomarker-labeled RGD combines with αvβ3, the signal can be visualized in vitro using equipment to clearly distinguish the lesion from the surrounding tissue. This conclusion indicates that clinicians can judge the progression of PCa by detecting the expression of αvβ3 and its location in patients and can predict whether the tumor is at risk of bone metastasis if necessary.…”