Two cases of early recurrence after transabdominal preperitoneal inguinal hernia repair

We performed transabdominal preperitoneal inguinal hernia repair in 46 patients (58 diseases), two of whom experienced early recurrence after mesh repair. Case 1 was a 76‐year‐old man with a bilateral inguinal hernia (recurrence site, left indirect hernia) after appendectomy. The recurrence occurred 1 month after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using the direct Kugel ® patch with an anterior technique. Case 2 was a 79‐year‐old man with a bilateral inguinal hernia (recurrence site, right direct hernia with an orifice >3 cm) after appendectomy. The recurrence occurred 3 months after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using an ULTRAPRO ® Plug with an anterior technique under laparoscopic observation. We believe the recurrences resulted from insufficient internal exfoliation and fixation affected by complicated exfoliation of the preperitoneal space with omental adhesion after intraperitoneal surgery.     

Synthesis and evaluation of PET probes for the imaging of I2 imidazoline receptors in peripheral tissues

IntroductionTo explore the possible use of positron emission tomography (PET) probes for imaging of I₂-imidazoline receptors (I₂Rs) in peripheral tissues, we labeled two new I₂R ligands, 2-[2-(o-tolyl)vinyl]-4,5-dihydro-1H-imidazole (K_i for I₂Rs, 3.7 nM) and 2-[2-(o-tolyl)ethyl]-4,5-dihydro-1H-imidazole (K_i for I₂Rs, 1.7 nM) with ¹¹C ([¹¹C]metrazoline and [¹¹C]TEIMD), respectively, and evaluated these ligands and the recently developed I₂R ligand 2-[3-fluoro-[4-¹¹C]tolyl]-4,5-dihydro-1H-imidazole ([¹¹C]FTIMD) by in vivo studies.Methods[¹¹C]Metrazoline and [¹¹C]TEIMD were prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [¹¹C]methyl iodide. Their biodistribution in mice was investigated by tissue dissection. In addition, PET scans and metabolite analysis were performed.Results[¹¹C]Metrazoline and [¹¹C]TEIMD were successfully synthesized with a suitable radioactivity for injection. In the liver and pancreas expressing I₂Rs, coinjection with the high-affinity I₂R ligand, BU224, induced a reduction in the radioactivity level at 30 min after injection of [¹¹C]metrazoline and [¹¹C]FTIMD. However, the radioactivity level after injection of [¹¹C]TEIMD was unchanged. In the PET study, coinjection with BU224 induced a decrease in the radioactivity level in the liver and pancreas after more than 15 min of injection of [¹¹C]metrazoline and [¹¹C]FTIMD as compared with the results obtained for controls. In metabolite analysis, coinjection with BU224 induced a significant reduction in the percentage of unchanged [¹¹C]metrazoline at 30 min after injection as compared with that in the control, although no significant difference was observed in the percentage of unchanged [¹¹C]FTIMD.Conclusion[¹¹C]Metrazoline may be a more useful PET probe than [¹¹C]FTIMD for imaging of I₂Rs in peripheral tissues.     

PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2-imidazoline receptors binding in rat brains

IntroductionWe recently developed a selective ¹¹C-labeled I₂-imidazoline receptor (I₂R) ligand, 2-(3-fluoro-4-[¹¹C]tolyl)-4,5-dihydro-1H-imidazole ([¹¹C]FTIMD). [¹¹C]FTIMD showed specific binding to I₂Rs in rat brains having a high density of I₂R, as well as to I₂Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [¹¹C]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for I₂R in rat brains, we synthesized [¹¹C]FTIMD with ultra-high specific activity and evaluated its binding.Methods[¹¹C]FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [¹¹C]methyl iodide, which was produced by iodination of [¹¹C]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated.Results[¹¹C]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470±1660 GBq/μmol at end of synthesis, n=11) for injection. In the PET study, distribution volume (V_T) values in all the brain regions investigated whether I₂R expression was greatly reduced in BU224-pretreatead rats compared with control rats (29–45% decrease). Differences in V_T values between control and BU224-pretreated rats using [¹¹C]FTIMD with ultra-high specific activity were greater than those using [¹¹C]FTIMD with normal specific activity (17–34% decrease) in all brain regions investigated.ConclusionQuantitative PET using [¹¹C]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I₂R expression in the brain.     

Blood flow dependence of the intratumoral distribution of peripheral benzodiazepine receptor binding in intact mouse fibrosarcoma

The intratumoral distribution of [¹¹C]AC-5216 binding, a novel peripheral benzodiazepine receptor (PBR) ligand, was examined by autoradiography both in vitro and in vivo using a murine fibrosarcoma model. The regional distribution of [¹¹C]AC-5216 in a tumor in vivo was significantly heterogeneous; the uptake of [¹¹C]AC-5216 was comparatively higher in the outer rim of the tumor and was lower in the central area. In contrast, the images obtained following the injection of [¹¹C]AC-5216 with a large amount of nonlabeled PK11195 showed a relatively homogeneous distribution, suggesting that [¹¹C]AC-5216 uptake represented specific binding to PBRs. In vitro autoradiograms of [¹¹C]AC-5216 binding were also obtained using the section of the fibrosarcoma that was the same as that used to examine in vivo binding. In vitro autoradiographic binding images showed homogeneous distribution, and significant discrepancies of the intratumoral distribution of [¹¹C]AC-5216 were observed between in vivo and in vitro images. The in vivo images of [¹¹C]AC-5216 uptake, compared with those of [¹⁴C]iodoantipyrine uptake, obtained by dual autoradiography to evaluate the influence of blood flow revealed the similar intratumoral distributions of both tracers. These results indicate that the delivery process from the plasma to the tumor might be the rate-limiting step for the intratumoral distribution of PBR binding in vivo in a fibrosarcoma model.     

Molecular imaging of ectopic metabotropic glutamate 1 receptor in melanoma with a positron emission tomography radioprobe 18F‐FITM

Oncoimaging using positron emission tomography (PET) with a specific radioprobe would facilitate individualized cancer management. Evidence indicates that ectopically expressed metabotropic glutamate 1 (mGlu1) receptor independently induces melanocyte carcinogenesis, and it is therefore becoming an important target for personalized diagnosis and treatment strategies for melanomas. Here, we report the development of an oncoprotein‐based PET imaging platform in melanomas for noninvasive visualization and quantification of mGlu1 with a novel mGlu1‐specific radioprobe, 4‐¹⁸F‐fluoro‐N‐[4‐[6‐(isopropyl amino)pyrimidin‐4‐yl]‐1,3‐thiazol‐2‐yl]‐N‐methylbenzamide (¹⁸F‐FITM). ¹⁸F‐FITM shows excellent pharmacokinetics, namely the dense and specific accumulation in mGlu1‐positive melanomas versus mGlu1‐negative hepatoma and normal tissues. Furthermore, the accumulation levels of radioactivity corresponded to the extent of tumor and to levels of mGlu1 protein expression in melanomas and melanoma metastasis. The ¹⁸F‐FITM PET imaging platform, as a noninvasive personalized diagnostic tool, is expected to open a new avenue for defining individualized therapeutic strategies, clinical trials, patient management and understanding mGlu1‐triggered oncologic events in melanomas.